Protein conformation and biomolecular condensates

Current Research in Structural Biology - Tập 4 - Trang 285-307 - 2022
Diego S. Vazquez1, Pamela L. Toledo1, Alejo R. Gianotti1, Mario R. Ermácora1
1Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes and Grupo de Biología Estructural y Biotecnología, IMBICE, CONICET, Universidad Nacional de Quilmes, Argentina

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Aarum, 2020, Enzymatic degradation of RNA causes widespread protein aggregation in cell and tissue lysates, EMBO Rep., 21, 10.15252/embr.201949585

Abyzov, 2022, Conformational dynamics of intrinsically disordered proteins regulate biomolecular condensate chemistry, Chem. Rev., 122, 6719, 10.1021/acs.chemrev.1c00774

Adamcik, 2018, Amyloid polymorphism in the protein folding and aggregation energy landscape, Angew. Chem. Int. Ed., 57, 8370, 10.1002/anie.201713416

Alberti, 2019, Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates, Cell, 176, 419, 10.1016/j.cell.2018.12.035

Alberti, 2021, Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing, Nat. Rev. Mol. Cell Biol., 22, 196, 10.1038/s41580-020-00326-6

André, 2020, Liquid--liquid phase separation in crowded environments, Int. J. Mol. Sci., 21, 5908, 10.3390/ijms21165908

Arakawa, 1985, Theory of protein solubility, 49, 10.1016/0076-6879(85)14005-X

Astbury, 1931, X-ray studies of the structure of hair, wool, and related fibres.-I. General, Philos. Trans. R. Soc. London, Ser. A, 75

Azaldegui, 2021, The emergence of phase separation as an organizing principle in bacteria, Biophys. J., 120, 1123, 10.1016/j.bpj.2020.09.023

Banani, 2016, Compositional control of phase-separated cellular bodies, Cell, 166, 651, 10.1016/j.cell.2016.06.010

Banani, 2017, Biomolecular condensates: organizers of cellular biochemistry, Nat. Rev. Mol. Cell Biol., 18, 285, 10.1038/nrm.2017.7

Banerjee, 2017, Reentrant phase transition drives dynamic substructure formation in ribonucleoprotein droplets, Angew. Chem., 129, 11512, 10.1002/ange.201703191

Banjade, 2014, Phase transitions of multivalent proteins can promote clustering of membrane receptors, Elife, 3, 10.7554/eLife.04123

Berland, 1992, Solid-liquid phase boundaries of lens protein solutions, Proc. Natl. Acad. Sci. USA, 89, 1214, 10.1073/pnas.89.4.1214

Bernal, 1934, X-ray photographs of crystalline pepsin, Nature, 133, 794, 10.1038/133794b0

Berry, 2018, Physical principles of intracellular organization via active and passive phase transitions, Rep. Prog. Phys., 81, 10.1088/1361-6633/aaa61e

Beutel, 2019, Phase separation of zonula occludens proteins drives formation of tight junctions, Cell, 179, 923, 10.1016/j.cell.2019.10.011

Bhopatkar, 2022, Charge and redox states modulate granulin-TDP-43 coacervation toward phase separation or aggregation, Biophys. J., 121, 2107, 10.1016/j.bpj.2022.04.034

Biswas, 2021, Thermodynamics of droplets undergoing liquid-liquid phase separation, bioRxiv

Boeynaems, 2018, Protein phase separation: a new phase in cell biology, Trends Cell Biol., 28, 420, 10.1016/j.tcb.2018.02.004

Boisvert, 2007, The multifunctional nucleolus, Nat. Rev. Mol. Cell Biol., 8, 574, 10.1038/nrm2184

Bolognesi, 2016, A concentration-dependent liquid phase separation can cause toxicity upon increased protein expression, Cell Rep., 16, 222, 10.1016/j.celrep.2016.05.076

Botterbusch, 2021, Interactions between phase-separated liquids and membrane surfaces, Appl. Sci., 11, 10.3390/app11031288

Brady, 2017, Structural and hydrodynamic properties of an intrinsically disordered region of a germ cell-specific protein on phase separation, Proc. Natl. Acad. Sci. USA, 114, 10.1073/pnas.1706197114

Brangwynne, 2009, Germline P granules are liquid droplets that localize by controlled dissolution/condensation, Science, 324, 1729, 10.1126/science.1172046

Brocca, 2020, Liquid–liquid phase separation by intrinsically disordered protein regions of viruses: roles in viral life cycle and control of virus–host interactions, Int. J. Mol. Sci., 10.3390/ijms21239045

Broide, 1991, Binary-liquid phase separation of lens protein solutions, Proc. Natl. Acad. Sci. USA, 88, 5660, 10.1073/pnas.88.13.5660

Burke, 2015, Residue-by-residue view of in vitro FUS granules that bind the C-terminal domain of RNA polymerase II, Mol. Cell, 60, 231, 10.1016/j.molcel.2015.09.006

Cardinaux, 2007, Interplay between spinodal decomposition and glass formation in proteins exhibiting short-range attractions, Phys. Rev. Lett., 99, 10.1103/PhysRevLett.99.118301

Celetti, 2020, The liquid state of FG-nucleoporins mimics permeability barrier properties of nuclear pore complexes, J. Cell Biol., 219, 10.1083/jcb.201907157

Chan, 2012, Anisotropy of the coulomb interaction between folded proteins: consequences for mesoscopic aggregation of lysozyme, Biophys. J., 102, 1934, 10.1016/j.bpj.2012.03.025

Chan, 2019, A mechanism for reversible mesoscopic aggregation in liquid solutions, Nat. Commun., 10, 1, 10.1038/s41467-019-10270-5

Chattaraj, 2021, The solubility product extends the buffering concept to heterotypic biomolecular condensates, Elife, 10, 10.7554/eLife.67176

Chatterjee, 2022, Reversible kinetic trapping of FUS biomolecular condensates, Adv. Sci., 9, 10.1002/advs.202104247

Cho, 2018, Mediator and RNA polymerase II clusters associate in transcription-dependent condensates, Science, 361, 412, 10.1126/science.aar4199

Choi, 2020, Physical principles underlying the complex biology of intracellular phase transitions, Annu. Rev. Biophys., 49, 107, 10.1146/annurev-biophys-121219-081629

Chong, 2016, Liquid–liquid phase separation in cellular signaling systems, Curr. Opin. Struct. Biol., 41, 180, 10.1016/j.sbi.2016.08.001

Chong, 2021, Towards decoding the sequence-based grammar governing the functions of intrinsically disordered protein regions, J. Mol. Biol., 433, 10.1016/j.jmb.2020.11.023

Chu, 2022, Prediction of liquid-liquid phase separating proteins using machine learning, BMC Bioinf., 23, 1, 10.1186/s12859-022-04599-w

Correll, 2019, The nucleolus: a multiphase condensate balancing ribosome synthesis and translational capacity in health, aging and ribosomopathies, Cells, 8, 869, 10.3390/cells8080869

Curtis, 2001, McMillan--Mayer solution thermodynamics for a protein in a mixed solvent, Fluid Phase Equil., 192, 131, 10.1016/S0378-3812(01)00635-5

Das, 2022, Zn-dependent structural transition of SOD1 modulates its ability to undergo liquid-liquid phase separation, bioRxiv

Dignon, 2020, Biomolecular phase separation: from molecular driving forces to macroscopic properties, Annu. Rev. Phys. Chem., 71, 53, 10.1146/annurev-physchem-071819-113553

Ditlev, 2021, Membrane-associated phase separation: organization and function emerge from a two-dimensional milieu, J. Mol. Cell Biol., 13, 319, 10.1093/jmcb/mjab010

Ditlev, 2018, Who's in and who's out—compositional control of biomolecular condensates, J. Mol. Biol., 430, 4666, 10.1016/j.jmb.2018.08.003

Dodson, 1998, The role of assembly in insulin's biosynthesis, Curr. Opin. Struct. Biol., 8, 189, 10.1016/S0959-440X(98)80037-7

Dumetz, 2008, Protein phase behavior in aqueous solutions: crystallization, liquid-liquid phase separation, gels, and aggregates, Biophys. J., 94, 570, 10.1529/biophysj.107.116152

Elbaum-Garfinkle, 2015, The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics, Proc. Natl. Acad. Sci. USA, 112, 7189, 10.1073/pnas.1504822112

Etibor, 2021, Liquid biomolecular condensates and viral lifecycles: review and perspectives, Viruses, 13, 366, 10.3390/v13030366

Feng, 2021, Liquid--liquid phase separation in biology: specific stoichiometric molecular interactions vs promiscuous interactions mediated by disordered sequences, Biochemistry, 60, 2397, 10.1021/acs.biochem.1c00376

Flecken, 2020, Dual functions of a rubisco activase in metabolic repair and recruitment to carboxysomes, Cell, 183, 457, 10.1016/j.cell.2020.09.010

Flory, 1942, Thermodynamics of high polymer solutions, J. Chem. Phys., 10, 51, 10.1063/1.1723621

Folkmann, 2021, Regulation of biomolecular condensates by interfacial protein clusters, Science, 373, 1218, 10.1126/science.abg7071

Fomicheva, 2021, From prions to stress granules: defining the compositional features of prion-like domains that promote different types of assemblies, Int. J. Mol. Sci., 22, 1251, 10.3390/ijms22031251

Forman-Kay, 2018, Phase separation in biology and disease, J. Mol. Biol., 430, 4603, 10.1016/j.jmb.2018.09.006

Fox, 2018, Paraspeckles: where long noncoding RNA meets phase separation, Trends Biochem. Sci., 43, 124, 10.1016/j.tibs.2017.12.001

Franzmann, 2018, Phase separation of a yeast prion protein promotes cellular fitness, Science, 359, 10.1126/science.aao5654

Frey, 2007, A saturated FG-repeat hydrogel can reproduce the permeability properties of nuclear pore complexes, Cell, 130, 512, 10.1016/j.cell.2007.06.024

Fritsch, 2021, Local thermodynamics govern formation and dissolution of Caenorhabditis elegans P granule condensates, Proc. Natl. Acad. Sci. USA, 118, 10.1073/pnas.2102772118

Frottin, 2019, The nucleolus functions as a phase-separated protein quality control compartment, Science, 365, 342, 10.1126/science.aaw9157

Gaglia, 2020, HSF1 phase transition mediates stress adaptation and cell fate decisions, Nat. Cell Biol., 22, 151, 10.1038/s41556-019-0458-3

Galkin, 2007, Two-step mechanism of homogeneous nucleation of sickle cell hemoglobin polymers, Biophys. J., 93, 902, 10.1529/biophysj.106.103705

Georgalis, 1999, Ordering of fractal clusters in crystallizing lysozyme solutions, J. Am. Chem. Soc., 121, 1627, 10.1021/ja982407y

Ghosh, 2021, Can coacervation unify disparate hypotheses in the origin of cellular life?, Curr. Opin. Colloid Interface Sci., 52, 10.1016/j.cocis.2020.101415

Giannattasio, 1975, Molecular organization of rat prolactin granules: in vitro stability of intact and "membraneless" granules, J. Cell Biol., 64, 246, 10.1083/jcb.64.1.246

Gibson, 2019, Organization of chromatin by intrinsic and regulated phase separation, Cell, 179, 470, 10.1016/j.cell.2019.08.037

Gliko, 2005, Dense liquid droplets as a step source for the crystallization of lumazine synthase, J. Cryst. Growth, 275, e1409, 10.1016/j.jcrysgro.2004.11.291

Gliko, 2007, Metastable liquid clusters in super-and undersaturated protein solutions, J. Phys. Chem. B, 111, 3106, 10.1021/jp068827o

Goetz, 2020, Visualizing molecular architectures of cellular condensates: hints of complex coacervation scenarios, Dev. Cell, 55, 97, 10.1016/j.devcel.2020.09.003

Gomes, 2019, The molecular language of membraneless organelles, J. Biol. Chem., 294, 7115, 10.1074/jbc.TM118.001192

Grouazel, 2006, Exploring bovine pancreatic trypsin inhibitor phase transitions, J. Phys. Chem. B, 110, 19664, 10.1021/jp0627123

Guillén-Boixet, 2020, RNA-induced conformational switching and clustering of G3BP drive stress granule assembly by condensation, Cell, 181, 346, 10.1016/j.cell.2020.03.049

Guin, 2019, Weak chemical interactions that drive protein evolution: crowding, sticking, and quinary structure in folding and function, Chem. Rev., 119, 10691, 10.1021/acs.chemrev.8b00753

Guo, 2018, Nuclear-import receptors reverse aberrant phase transitions of RNA-binding proteins with prion-like domains, Cell, 173, 677, 10.1016/j.cell.2018.03.002

Guo, 2022, Localized proteasomal degradation: from the nucleus to cell periphery, Biomolecules, 12, 229, 10.3390/biom12020229

Haas, 1999, Understanding protein crystallization on the basis of the phase diagram, J. Cryst. Growth, 196, 388, 10.1016/S0022-0248(98)00831-8

Hardenberg, 2020, Widespread occurrence of the droplet state of proteins in the human proteome, Proc. Natl. Acad. Sci. USA, 117, 33254, 10.1073/pnas.2007670117

Harpaz, 1994, Volume changes on protein folding, Structure, 2, 641, 10.1016/S0969-2126(00)00065-4

Hazra, 2021, Biophysics of phase separation of disordered proteins is governed by balance between short-and long-range interactions, J. Phys. Chem. B, 125, 2202, 10.1021/acs.jpcb.0c09975

Hilser, 1996, The enthalpy change in protein folding and binding: refinement of parameters for structure-based calculations, Proteins: Struct., Funct., Bioinf., 26, 123, 10.1002/(SICI)1097-0134(199610)26:2<123::AID-PROT2>3.0.CO;2-H

Hofweber, 2018, Phase separation of FUS is suppressed by its nuclear import receptor and arginine methylation, Cell, 173, 706, 10.1016/j.cell.2018.03.004

Holehouse, 2018, Collapse transitions of proteins and the interplay among backbone, sidechain, and solvent interactions, Annu. Rev. Biophys., 47, 19, 10.1146/annurev-biophys-070317-032838

Holehouse, 2018, Functional implications of intracellular phase transitions, Biochemistry, 57, 2415, 10.1021/acs.biochem.7b01136

Honda, 1999, Lectures on phase transition and the renormalization group lectures on phase transition and the renormalization group, 1992, J. Phys. Soc. Japan, 68, 3236, 10.1143/JPSJ.68.3236

Horvath, 2020, Sequence-based prediction of protein binding mode landscapes, PLoS Comput. Biol., 16, 10.1371/journal.pcbi.1007864

Huggins, 1941, Solutions of long chain compounds, J. Chem. Phys., 9, 440, 10.1063/1.1750930

Hughes, 2021, Prevalence and species distribution of the low-complexity, amyloid-like, reversible, kinked segment structural motif in amyloid-like fibrils, J. Biol. Chem., 297, 10.1016/j.jbc.2021.101194

Hyman, 2014, Liquid-liquid phase separation in biology, Annu. Rev. Cell Dev. Biol., 30, 39, 10.1146/annurev-cellbio-100913-013325

Ikenoue, 2014, Heat of supersaturation-limited amyloid burst directly monitored by isothermal titration calorimetry, Proc. Natl. Acad. Sci. USA, 111, 6654, 10.1073/pnas.1322602111

Iserman, 2020, Genomic RNA elements drive phase separation of the SARS-CoV-2 nucleocapsid, Mol. Cell, 80, 1078, 10.1016/j.molcel.2020.11.041

Ishimoto, 1977, Critical behavior of a binary mixture of protein and salt water, Phys. Rev. Lett., 39, 474, 10.1103/PhysRevLett.39.474

Jawerth, 2020, Protein condensates as aging Maxwell fluids, Science, 370, 1317, 10.1126/science.aaw4951

Kamagata, 2021, Single-molecule microscopy meets molecular dynamics simulations for characterizing the molecular action of proteins on DNA and in liquid condensates, Front. Mol. Biosci., 1139

Kamagata, 2021, Molecular principles of recruitment and dynamics of guest proteins in liquid droplets, Sci. Rep., 11, 1, 10.1038/s41598-021-98955-0

Kamagata, 2020, Liquid-like droplet formation by tumor suppressor p53 induced by multivalent electrostatic interactions between two disordered domains, Sci. Rep., 10, 1, 10.1038/s41598-020-57521-w

Kang, 2018, ATP enhances at low concentrations but dissolves at high concentrations liquid-liquid phase separation (LLPS) of ALS/FTD-causing FUS, Biochem. Biophys. Res. Commun., 504, 545, 10.1016/j.bbrc.2018.09.014

Kar, 2022

Kardos, 2004, Direct measurement of the thermodynamic parameters of amyloid formation by isothermal titration calorimetry, J. Biol. Chem., 279, 55308, 10.1074/jbc.M409677200

Kato, 2012, Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels, Cell, 149, 753, 10.1016/j.cell.2012.04.017

Kato, 2019, Redox state controls phase separation of the yeast ataxin-2 protein via reversible oxidation of its methionine-rich low-complexity domain, Cell, 177, 711, 10.1016/j.cell.2019.02.044

Keating, 2012, Aqueous phase separation as a possible route to compartmentalization of biological molecules, Acc. Chem. Res., 45, 2114, 10.1021/ar200294y

Keber, 2021, Evidence for widespread cytoplasmic structuring into mesoscopic condensates, bioRxiv

Kelley, 2021, Amphiphilic proteins coassemble into multiphasic condensates and act as biomolecular surfactants, Proc. Natl. Acad. Sci. USA, 118, 10.1073/pnas.2109967118

Kienzle, 2014, Secretory cargo sorting at the trans-Golgi network, Trends Cell Biol., 24, 584, 10.1016/j.tcb.2014.04.007

Kiledjian, 1992, Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box, EMBO J., 11, 2655, 10.1002/j.1460-2075.1992.tb05331.x

Kim, 2021, Interaction hot spots for phase separation revealed by NMR studies of a CAPRIN1 condensed phase, Proc. Natl. Acad. Sci. USA, 118

King, 2012, The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease, Brain Res., 1462, 61, 10.1016/j.brainres.2012.01.016

Klaips, 2018, Pathways of cellular proteostasis in aging and disease, J. Cell Biol., 217, 51, 10.1083/jcb.201709072

Klein, 2020, Partitioning of cancer therapeutics in nuclear condensates, Science, 368, 1386, 10.1126/science.aaz4427

Knee, 2009, Real time monitoring of sickle cell hemoglobin fiber formation by UV resonance Raman spectroscopy, Biochemistry, 48, 9903, 10.1021/bi901352m

Koopman, 2022, How do protein aggregates escape quality control in neurodegeneration?, Trends Neurosci., 45, 257, 10.1016/j.tins.2022.01.006

Kuechler, 2022, GraPES: the granule protein enrichment server for prediction of biological condensate constituents, Nucleic Acids Res., 50, W384, 10.1093/nar/gkac279

Kumar, 2017, Hitchhiking vesicular transport routes to the vacuole: amyloid recruitment to the Insoluble Protein Deposit (IPOD), Prion, 11, 71, 10.1080/19336896.2017.1293226

Kundra, 2017, Protein homeostasis of a metastable subproteome associated with Alzheimer's disease, Proc. Natl. Acad. Sci. USA, 114, E5703, 10.1073/pnas.1618417114

Ladenstein, 2013, The lumazine synthase/riboflavin synthase complex: shapes and functions of a highly variable enzyme system, FEBS J., 280, 2537, 10.1111/febs.12255

Lafontaine, 2021, The nucleolus as a multiphase liquid condensate, Nat. Rev. Mol. Cell Biol., 22, 165, 10.1038/s41580-020-0272-6

Lagier-Tourenne, 2010, TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration, Hum. Mol. Genet., 19, R46, 10.1093/hmg/ddq137

Lancaster, 2014, PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition, Bioinformatics, 30, 2501, 10.1093/bioinformatics/btu310

Latham, 2022, Unifying coarse-grained force fields for folded and disordered proteins, Curr. Opin. Struct. Biol., 72, 63, 10.1016/j.sbi.2021.08.006

Latonen, 2019, Phase-to-phase with nucleoli–stress responses, protein aggregation and novel roles of RNA, Front. Cell. Neurosci., 13, 151, 10.3389/fncel.2019.00151

Lawrence, 1993, Shape complementarity at protein/protein interfaces, J. Mol. Biol., 234, 946, 10.1006/jmbi.1993.1648

Lee, 2020, Molecular structure and interactions within amyloid-like fibrils formed by a low-complexity protein sequence from FUS, Nat. Commun., 11, 1, 10.1038/s41467-020-19512-3

Lei, 2021, Protein quality control by the proteasome and autophagy: a regulatory role of ubiquitin and liquid-liquid phase separation, Matrix Biol., 100–101, 9, 10.1016/j.matbio.2020.11.003

Lemos, 2020, Identification of small molecules that modulate mutant p53 condensation, iScience, 23, 10.1016/j.isci.2020.101517

Lerman, 1966, Properties of a cryoprotein in the ocular lens, Biochem. Biophys. Res. Commun., 22, 57, 10.1016/0006-291X(66)90602-4

Levine, 2019, Targeting therapies for the p53 protein in cancer treatments, Annu. Rev. Cell Biol., 3, 21, 10.1146/annurev-cancerbio-030518-055455

Li, 2018, Phase behavior and salt partitioning in polyelectrolyte complex coacervates, Macromolecules, 51, 2988, 10.1021/acs.macromol.8b00238

Li, 2012, Phase transitions in the assembly of multivalent signalling proteins, Nature, 483, 336, 10.1038/nature10879

Li, 2011, The use of dynamic light scattering and Brownian microscopy to characterize protein aggregation, Rev. Sci. Instrum., 82, 10.1063/1.3592581

Li, 2012, Ostwald-like ripening of the anomalous mesoscopic clusters in protein solutions, J. Phys. Chem. B, 116, 10657, 10.1021/jp303316s

Liang, 2018, Conformational evolution of polymorphic amyloid assemblies, Curr. Opin. Struct. Biol., 51, 135, 10.1016/j.sbi.2018.04.004

Lin, 2022, A two-component protein condensate of the EGFR cytoplasmic tail and Grb2 regulates Ras activation by SOS at the membrane, Proc. Natl. Acad. Sci. USA, 119, 10.1073/pnas.2122531119

Lin, 2016, Toxic PR poly-dipeptides encoded by the C9orf72 repeat expansion target LC domain polymers, Cell, 167, 789, 10.1016/j.cell.2016.10.003

Lopez, 2021, Deconstructing virus condensation, PLoS Pathog., 17, 10.1371/journal.ppat.1009926

Lyon, 2021, A framework for understanding the functions of biomolecular condensates across scales, Nat. Rev. Mol. Cell Biol., 22, 215, 10.1038/s41580-020-00303-z

Machyna, 2013, Cajal bodies: where form meets function, Wiley Interdiscip. Rev. RNA, 4, 17, 10.1002/wrna.1139

Mackenzie, 2017, TIA1 mutations in amyotrophic lateral sclerosis and frontotemporal dementia promote phase separation and alter stress granule dynamics, Neuron, 95, 808, 10.1016/j.neuron.2017.07.025

Maes, 2015, Do protein crystals nucleate within dense liquid clusters?, Acta Crystallogr. Sect. F Struct. Biol. Commun., 71, 815, 10.1107/S2053230X15008997

Maharana, 2018, RNA buffers the phase separation behavior of prion-like RNA binding proteins, Science, 360, 918, 10.1126/science.aar7366

Maji, 2009, Functional amyloids as natural storage of peptide hormones in pituitary secretory granules, Science, 325, 328, 10.1126/science.1173155

Malay, 2020, Spider silk self-assembly via modular liquid-liquid phase separation and nanofibrillation, Sci. Adv., 6, 10.1126/sciadv.abb6030

Manoharan, 2015, Colloidal matter: packing, geometry, and entropy, Science, 349, 10.1126/science.1253751

Martin, 2020, Valence and patterning of aromatic residues determine the phase behavior of prion-like domains, Science, 367, 694, 10.1126/science.aaw8653

Martin, 2018, Relationship of sequence and phase separation in protein low-complexity regions, Biochemistry, 57, 2478, 10.1021/acs.biochem.8b00008

Martin, 2021, Interplay of folded domains and the disordered low-complexity domain in mediating hnRNPA1 phase separation, Nucleic Acids Res., 49, 2931, 10.1093/nar/gkab063

Mathieu, 2020, Beyond aggregation: pathological phase transitions in neurodegenerative disease, Science, 370, 56, 10.1126/science.abb8032

Matthews, 1968, Solvent content of protein crystals, J. Mol. Biol., 33, 491, 10.1016/0022-2836(68)90205-2

McAlary, 2020, Amyotrophic lateral sclerosis: proteins, proteostasis, prions, and promises, Front. Cell. Neurosci., 14, 10.3389/fncel.2020.581907

McCall, 2020, Quantitative phase microscopy enables precise and efficient determination of biomolecular condensate composition, bioRxiv

McManus, 2016, The physics of protein self-assembly, Curr. Opin. Colloid Interface Sci., 22, 73, 10.1016/j.cocis.2016.02.011

Mészáros, 2020, PhaSePro: the database of proteins driving liquid-liquid phase separation, Nucleic Acids Res., 48, D360

Michael, 1987, Studies on the molecular organization of rat insulin secretory granules, J. Biol. Chem., 262, 16531, 10.1016/S0021-9258(18)49288-5

Milkovic, 2020, Determination of protein phase diagrams by centrifugation, 685

Milovanovic, 2018, A liquid phase of synapsin and lipid vesicles, Science, 361, 604, 10.1126/science.aat5671

Miskei, 2020, Sequence-based prediction of fuzzy protein interactions, J. Mol. Biol., 432, 2289, 10.1016/j.jmb.2020.02.017

Mittal, 2018, Sequence-to-conformation relationships of disordered regions tethered to folded domains of proteins, J. Mol. Biol., 430, 2403, 10.1016/j.jmb.2018.05.012

Mohanty, 2022, Principles governing the phase separation of multidomain proteins, Biochemistry, 10.1021/acs.biochem.2c00210

Molliex, 2015, Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization, Cell, 163, 123, 10.1016/j.cell.2015.09.015

Monahan, 2017, Phosphorylation of the FUS low-complexity domain disrupts phase separation, aggregation, and toxicity, EMBO J., 36, 2951, 10.15252/embj.201696394

Muiznieks, 2018, Role of liquid--liquid phase separation in assembly of elastin and other extracellular matrix proteins, J. Mol. Biol., 430, 4741, 10.1016/j.jmb.2018.06.010

Mukherjee, 2020, CL6mN: rationally designed optogenetic photoswitches with tunable dissociation dynamics, ACS Synth. Biol., 9, 2274, 10.1021/acssynbio.0c00362

Murakami, 2015, ALS/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs RNP granule function, Neuron, 88, 678, 10.1016/j.neuron.2015.10.030

Murray, 2017, Structure of FUS protein fibrils and its relevance to self-assembly and phase separation of low-complexity domains, Cell, 171, 615, 10.1016/j.cell.2017.08.048

Murthy, 2019, Molecular interactions underlying liquid-liquid phase separation of the FUS low-complexity domain, Nat. Struct. Mol. Biol., 26, 637, 10.1038/s41594-019-0250-x

Muschol, 1997, Liquid–liquid phase separation in supersaturated lysozyme solutions and associated precipitate formation/crystallization, J. Chem. Phys., 107, 1953, 10.1063/1.474547

Nakashima, 2019, Biomolecular chemistry in liquid phase separated compartments, Front. Mol. Biosci., 6, 10.3389/fmolb.2019.00021

Nassar, 2021, The protein folding problem: the role of theory, J. Mol. Biol., 433, 10.1016/j.jmb.2021.167126

Nesterov, 2021, Liquid-liquid phase separation as a common organizing principle of intracellular space and biomembranes providing dynamic adaptive responses, Biochim. Biophys. Acta, Mol. Cell Res., 1868, 10.1016/j.bbamcr.2021.119102

Nikfarjam, 2019, Irreversible nature of mesoscopic aggregates in lysozyme solutions, Colloid J., 81, 546, 10.1134/S1061933X19050090

Ning, 2020, DrLLPS: a data resource of liquid--liquid phase separation in eukaryotes, Nucleic Acids Res., 48, D288, 10.1093/nar/gkz1027

Nikolic, 2017, Negri bodies are viral factories with properties of liquid organelles, Nat. Commun., 8, 58, 10.1038/s41467-017-00102-9

Noji, 2021, Breakdown of supersaturation barrier links protein folding to amyloid formation, Commun. Biol., 4, 1, 10.1038/s42003-020-01641-6

Nott, 2015, Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles, Mol. Cell, 57, 936, 10.1016/j.molcel.2015.01.013

Nusse, 2017, Wnt β-catenin signaling, disease, and emerging therapeutic modalities, Cell, 169, 985, 10.1016/j.cell.2017.05.016

Oh, 2022, The regional sequestration of heterochromatin structural proteins is critical to form and maintain silent chromatin, Epigenet. Chromatin, 15, 1, 10.1186/s13072-022-00435-w

Orlando, 2019, Computational identification of prion-like RNA-binding proteins that form liquid phase-separated condensates, Bioinformatics, 35, 4617, 10.1093/bioinformatics/btz274

Orti, 2021, Insight into membraneless organelles and their associated proteins: drivers, Clients and Regulators, Comput. Struct. Biotechnol. J., 19, 3964, 10.1016/j.csbj.2021.06.042

Overbeek, 1957, Phase separation in polyelectrolyte solutions. Theory of complex coacervation, J. Cell. Comp. Physiol., 49, 7, 10.1002/jcp.1030490404

Pan, 2007, Metastable mesoscopic clusters in solutions of sickle-cell hemoglobin, Biophys. J., 92, 267, 10.1529/biophysj.106.094854

Pan, 2010, Origin of anomalous mesoscopic phases in protein solutions, J. Phys. Chem. B, 114, 7620, 10.1021/jp100617w

Pancsa, 2021, Computational resources for identifying and describing proteins driving liquid–liquid phase separation, Briefings Bioinf., 22, 10.1093/bib/bbaa408

Parchure, 2021, Liquid-liquid phase separation facilitates the biogenesis of secretory storage granules, bioRxiv

Parmar, 2009, Hydration and hydrodynamic interactions of lysozyme: effects of chaotropic versus kosmotropic ions, Biophys. J., 97, 590, 10.1016/j.bpj.2009.04.045

Parry, 2015, Functional amyloid signaling via the inflammasome, necrosome, and signalosome: new therapeutic targets in heart failure, Front. Cardiovasc. Med., 2, 25, 10.3389/fcvm.2015.00025

Patel, 2015, A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation, Cell, 162, 1066, 10.1016/j.cell.2015.07.047

Pattanayak, 2020, Daily cycles of reversible protein condensation in cyanobacteria, Cell Rep., 32, 10.1016/j.celrep.2020.108032

Pedley, 2022, Purine biosynthetic enzymes assemble into liquid-like condensates dependent on the activity of chaperone protein HSP90, J. Biol. Chem., 298, 10.1016/j.jbc.2022.101845

Pedrote, 2020, Oncogenic gain of function in glioblastoma is linked to mutant p53 amyloid oligomers, iScience, 23, 10.1016/j.isci.2020.100820

Peeples, 2021, Mechanistic dissection of increased enzymatic rate in a phase-separated compartment, Nat. Chem. Biol., 17, 693, 10.1038/s41589-021-00801-x

Peran, 2019, Unfolded states under folding conditions accommodate sequence-specific conformational preferences with random coil-like dimensions, Proc. Natl. Acad. Sci. USA, 116, 12301, 10.1073/pnas.1818206116

Peran, 2020, Molecular structure in biomolecular condensates, Curr. Opin. Struct. Biol., 60, 17, 10.1016/j.sbi.2019.09.007

Petronilho, 2021, Phase separation of p53 precedes aggregation and is affected by oncogenic mutations and ligands, Chem. Sci., 12, 7334, 10.1039/D1SC01739J

Petsev, 2003, Thermodynamic functions of concentrated protein solutions from phase equilibria, J. Phys. Chem. B, 107, 3921, 10.1021/jp0278317

Platten, 2015, Extended law of corresponding states for protein solutions, J. Chem. Phys., 142

Pombo, 2015, Three-dimensional genome architecture: players and mechanisms, Nat. Rev. Mol. Cell Biol., 16, 245, 10.1038/nrm3965

Posey, 2018, Profilin reduces aggregation and phase separation of huntingtin N-terminal fragments by preferentially binding to soluble monomers and oligomers, J. Biol. Chem., 293, 3734, 10.1074/jbc.RA117.000357

Poudyal, 2022, Liquid condensate is a common state of proteins and polypeptides at the regime of high intermolecular interactions, bioRxiv

Privalov, 2007, Thermodynamic problems in structural molecular biology, Pure Appl. Chem., 79, 1445, 10.1351/pac200779081445

Protter, 2016, Principles and properties of stress granules, Trends Cell Biol., 26, 668, 10.1016/j.tcb.2016.05.004

Qamar, 2018, FUS phase separation is modulated by a molecular chaperone and methylation of arginine cation-π interactions, Cell, 173, 720, 10.1016/j.cell.2018.03.056

Rai, 2018, Kinase-controlled phase transition of membraneless organelles in mitosis, Nature, 559, 211, 10.1038/s41586-018-0279-8

Rao, 2017, Numerous interactions act redundantly to assemble a tunable size of P bodies in Saccharomyces cerevisiae, Proc. Natl. Acad. Sci. USA, 114, E9569, 10.1073/pnas.1712396114

Ray, 2021, Spatiotemporal solidification of α-synuclein inside the liquid droplets, bioRxiv

Reichheld, 2017, Direct observation of structure and dynamics during phase separation of an elastomeric protein, Proc. Natl. Acad. Sci. USA, 114, E4408, 10.1073/pnas.1701877114

Riback, 2017, Stress-triggered phase separation is an adaptive, evolutionarily tuned response, Cell, 168, 1028, 10.1016/j.cell.2017.02.027

Riback, 2020, Composition-dependent thermodynamics of intracellular phase separation, Nature, 581, 209, 10.1038/s41586-020-2256-2

Roden, 2021, RNA contributions to the form and function of biomolecular condensates, Nat. Rev. Mol. Cell Biol., 22, 183, 10.1038/s41580-020-0264-6

Rouaud, 2020, Scaffolding proteins of vertebrate apical junctions: structure, functions and biophysics, Biochim. Biophys. Acta, Biomembr., 1862, 10.1016/j.bbamem.2020.183399

Rubinstein, 2003

Ruff, 2021, Ligand effects on phase separation of multivalent macromolecules, Proc. Natl. Acad. Sci. USA, 118, 10.1073/pnas.2017184118

Ruff, 2018, Advances in understanding stimulus-responsive phase behavior of intrinsically disordered protein polymers, J. Mol. Biol., 430, 4619, 10.1016/j.jmb.2018.06.031

Ryan, 2018, Mechanistic view of hnRNPA2 low-complexity domain structure, interactions, and phase separation altered by mutation and arginine methylation, Mol. Cell, 69, 465, 10.1016/j.molcel.2017.12.022

Saar, 2021, Learning the molecular grammar of protein condensates from sequence determinants and embeddings, Proc. Natl. Acad. Sci. USA, 118, 10.1073/pnas.2019053118

Safari, 2017, Polymorphism of lysozyme condensates, J. Phys. Chem. B, 121, 9091, 10.1021/acs.jpcb.7b05425

Safari, 2015, Differential dynamic microscopy of weakly scattering and polydisperse protein-rich clusters, Phys. Rev. E, 92, 10.1103/PhysRevE.92.042712

Safari, 2019, Anomalous dense liquid condensates host the nucleation of tumor suppressor p53 fibrils, iScience, 12, 342, 10.1016/j.isci.2019.01.027

Saha, 2016, Polar positioning of phase-separated liquid compartments in cells regulated by an mRNA competition mechanism, Cell, 166, 1572, 10.1016/j.cell.2016.08.006

Sanders, 2020, Competing protein-RNA interaction networks control multiphase intracellular organization, Cell, 181, 306, 10.1016/j.cell.2020.03.050

Sawaya, 2021, The expanding amyloid family: structure, stability, function, and pathogenesis, Cell, 184, 4857, 10.1016/j.cell.2021.08.013

Sawyer, 2019, vol. 10

Schaefer, 2019, Wnt/Beta-catenin signaling regulation and a role for biomolecular condensates, Dev. Cell, 48, 429, 10.1016/j.devcel.2019.01.025

Schmidt, 2021, Protein-based condensation mechanisms drive the assembly of RNA-rich P granules, Elife, 10, 10.7554/eLife.63698

Schmidt, 2016, Transport selectivity of nuclear pores, phase separation, and membraneless organelles, Trends Biochem. Sci., 41, 46, 10.1016/j.tibs.2015.11.001

Schubert, 2017, Real-time observation of protein dense liquid cluster evolution during nucleation in protein crystallization, Cryst. Growth Des., 17, 954, 10.1021/acs.cgd.6b01826

Schwayer, 2019, Mechanosensation of tight junctions depends on ZO-1 phase separation and flow, Cell, 179, 937, 10.1016/j.cell.2019.10.006

Seviour, 2020, Phase transitions by an abundant protein in the anammox extracellular matrix mediate cell-to-cell aggregation and biofilm formation, mBio, 11, 10.1128/mBio.02052-20

Shapiro, 2021, Protein phase separation arising from intrinsic disorder: first-principles to bespoke applications, J. Phys. Chem. B, 125, 6740, 10.1021/acs.jpcb.1c01146

Shin, 2017, Liquid phase condensation in cell physiology and disease, Science, 357, 10.1126/science.aaf4382

Siezen, 1985, Opacification of gamma-crystallin solutions from calf lens in relation to cold cataract formation, Proc. Natl. Acad. Sci. USA, 82, 1701, 10.1073/pnas.82.6.1701

Simon, 2017, Programming molecular self-assembly of intrinsically disordered proteins containing sequences of low complexity, Nat. Chem., 9, 509, 10.1038/nchem.2715

Sleutel, 2014, Role of clusters in nonclassical nucleation and growth of protein crystals, Proc. Natl. Acad. Sci. USA, 111, E546, 10.1073/pnas.1309320111

Snead, 2019, The control centers of biomolecular phase separation: how membrane surfaces, post-translational modifications, and active processes regulate condensation, Mol. Cell, 76, 295, 10.1016/j.molcel.2019.09.016

So, 2016, Revisiting supersaturation as a factor determining amyloid fibrillation, Curr. Opin. Struct. Biol., 36, 32, 10.1016/j.sbi.2015.11.009

Soranno, 2020, Physical basis of the disorder-order transition, Arch. Biochem. Biophys., 685, 10.1016/j.abb.2020.108305

Sosa, 2016, Biochemical, biophysical, and functional properties of ICA512/IA-2 RESP18 homology domain, Biochim. Biophys. Acta, Proteins Proteomics, 1864, 511, 10.1016/j.bbapap.2016.01.013

Spruijt, 2010, Binodal compositions of polyelectrolyte complexes, Macromolecules, 43, 6476, 10.1021/ma101031t

Su, 2016, Phase separation of signaling molecules promotes T cell receptor signal transduction, Science, 352, 595, 10.1126/science.aad9964

Sun, 2011, Molecular determinants and genetic modifiers of aggregation and toxicity for the ALS disease protein FUS/TLS, PLoS Biol., 9, 10.1371/journal.pbio.1000614

Taratuta, 1990, Liquid-liquid phase separation of aqueous lysozyme solutions: effects of pH and salt identity, J. Phys. Chem., 94, 2140, 10.1021/j100368a074

Tesei, 2021, Accurate model of liquid--liquid phase behavior of intrinsically disordered proteins from optimization of single-chain properties, Proc. Natl. Acad. Sci. USA, 118, 10.1073/pnas.2111696118

Thomson, 1987, Binary liquid phase separation and critical phenomena in a protein/water solution, Proc. Natl. Acad. Sci. USA, 84, 7079, 10.1073/pnas.84.20.7079

Tiwary, 2019, Protein phase separation in mitosis, Curr. Opin. Cell Biol., 60, 92, 10.1016/j.ceb.2019.04.011

Toledo, 2019, ICA512 RESP18 homology domain is a protein-condensing factor and insulin fibrillation inhibitor, J. Biol. Chem., 294, 8564, 10.1074/jbc.RA119.007607

Tompa, 2008, Fuzzy complexes: polymorphism and structural disorder in protein–protein interactions, Trends Biochem. Sci., 33, 2, 10.1016/j.tibs.2007.10.003

Torquato, 2018, Perspective: basic understanding of condensed phases of matter via packing models, J. Chem. Phys., 149

Tunyasuvunakool, 2021, Highly accurate protein structure prediction for the human proteome, Nature, 596, 590, 10.1038/s41586-021-03828-1

Turoverov, 2019, Stochasticity of biological soft matter: emerging concepts in intrinsically disordered proteins and biological phase separation, Trends Biochem. Sci., 44, 716, 10.1016/j.tibs.2019.03.005

Updike, 2011, P granules extend the nuclear pore complex environment in the C. elegans germ line, J. Cell Biol., 192, 939, 10.1083/jcb.201010104

Ura

Urosev, 2020, Phase separation of intrinsically disordered protein polymers mechanically stiffens fibrin clots, Adv. Funct. Mater., 30

Uversky, 2017, Protein intrinsic disorder-based liquid--liquid phase transitions in biological systems: complex coacervates and membrane-less organelles, Adv. Colloid Interface Sci., 239, 97, 10.1016/j.cis.2016.05.012

Uversky, 2010, Understanding protein non-folding, Biochim. Biophys. Acta, Proteins Proteomics, 1804, 1231, 10.1016/j.bbapap.2010.01.017

Uversky, 2019, Life in phases: intra-and inter-molecular phase transitions in protein solutions, Biomolecules, 9, 842, 10.3390/biom9120842

Van Der Lee, 2014, Classification of intrinsically disordered regions and proteins, Chem. Rev., 114, 6589, 10.1021/cr400525m

Vecchi, 2020, Proteome-wide observation of the phenomenon of life on the edge of solubility, Proc. Natl. Acad. Sci. USA, 117, 1015, 10.1073/pnas.1910444117

Vekilov, 2004, Dense liquid precursor for the nucleation of ordered solid phases from solution, Cryst. Growth Des., 4, 671, 10.1021/cg049977w

Vernon, 2018, Pi-Pi contacts are an overlooked protein feature relevant to phase separation, Elife, 7, 10.7554/eLife.31486

Vernon, 2019, First-generation predictors of biological protein phase separation, Curr. Opin. Struct. Biol., 58, 88, 10.1016/j.sbi.2019.05.016

Vorontsova, 2016, Characterization of the diffusive dynamics of particles with time-dependent asymmetric microscopy intensity profiles, Soft Matter, 12, 6926, 10.1039/C6SM00946H

Walker, 2015, More than one way to spin a crystallite: multiple trajectories through liquid crystallinity to solid silk, Proc. R. Soc. B Biol. Sci., 282

Walker, 2007, Huntington's disease, Lancet, 369, 218, 10.1016/S0140-6736(07)60111-1

Wang, 2019, Rubisco condensate formation by CcmM in β-carboxysome biogenesis, Nature, 566, 131, 10.1038/s41586-019-0880-5

Wang, 2018, A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins, Cell, 174, 688, 10.1016/j.cell.2018.06.006

Wang, 2022, LLPSDB v2.0: an updated database of proteins undergoing liquid--liquid phase separation in vitro, Bioinformatics, 38, 2010, 10.1093/bioinformatics/btac026

Warzecha, 2017, Mesoscopic solute-rich clusters in olanzapine solutions, Cryst. Growth Des., 17, 6668, 10.1021/acs.cgd.7b01299

Wei, 2017, Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles, Nat. Chem., 9, 1118, 10.1038/nchem.2803

Wilkins, 1999, Hydrodynamic radii of native and denatured proteins measured by pulse field gradient NMR techniques, Biochemistry, 38, 16424, 10.1021/bi991765q

Wolf, 2014, Effective interactions in protein--salt solutions approaching liquid–liquid phase separation, J. Mol. Liq., 200, 20, 10.1016/j.molliq.2014.08.006

Wong, 2020, NMR experiments for studies of dilute and condensed protein phases: application to the phase-separating protein CAPRIN1, J. Am. Chem. Soc., 142, 2471, 10.1021/jacs.9b12208

Woodruff, 2018, Organization and function of non-dynamic biomolecular condensates, Trends Biochem. Sci., 43, 81, 10.1016/j.tibs.2017.11.005

Wu, 2022, Interactions between membraneless condensates and membranous organelles at the presynapse: a phase separation view of synaptic vesicle cycle, J. Mol. Biol., 167629

Wunder, 2018, The phase separation underlying the pyrenoid-based microalgal Rubisco supercharger, Nat. Commun., 9, 1, 10.1038/s41467-018-07624-w

Wunderlich, 1999, A classification of molecules, phases, and transitions as recognized by thermal analysis, Thermochim. Acta, 340, 37, 10.1016/S0040-6031(99)00252-X

Xu, 2021, Review of liquid--liquid phase separation in crystallization: from fundamentals to application, Cryst. Growth Des., 21, 7306, 10.1021/acs.cgd.0c01376

Yadav, 2019, Protein misfolding diseases and therapeutic approaches, Curr. Protein Pept. Sci., 20, 1226, 10.2174/1389203720666190610092840

Yanagisawa, 2010, Unraveling the mechanism of elastic fiber assembly: the roles of short fibulins, Int. J. Biochem. Cell Biol., 42, 1084, 10.1016/j.biocel.2010.03.009

Yang, 2021, Mesoscopic protein-rich clusters host the nucleation of mutant p53 amyloid fibrils, Proc. Natl. Acad. Sci. USA, 118

Yang, 2020, G3BP1 is a tunable switch that triggers phase separation to assemble stress granules, Cell, 181, 325, 10.1016/j.cell.2020.03.046

Yang, 2017, An overview of pickering emulsions: solid-particle materials, classification, morphology, and applications, Front. Pharmacol., 8, 287, 10.3389/fphar.2017.00287

Yewdall, 2021, Coacervates as models of membraneless organelles, Curr. Opin. Colloid Interface Sci., 52, 10.1016/j.cocis.2020.101416

Ying, 1987, Overlap concentration of macromolecules in solution, Macromolecules, 20, 362, 10.1021/ma00168a023

Yoshizawa, 2020, Biological phase separation: cell biology meets biophysics, Biophys. Rev., 12, 519, 10.1007/s12551-020-00680-x

You, 2020, PhaSepDB: a database of liquid-liquid phase separation related proteins, Nucleic Acids Res., 48, D354, 10.1093/nar/gkz847

Youn, 2019, Properties of stress granule and P-body proteomes, Mol. Cell, 76, 286, 10.1016/j.molcel.2019.09.014

Yuan, 2019, Nucleation and growth of amino acid and peptide supramolecular polymers through liquid--liquid phase separation, Angew. Chem., 131, 18284, 10.1002/ange.201911782

Zang, 2021, Scaffolding protein CcmM directs multiprotein phase separation in β-carboxysome biogenesis, Nat. Struct. Mol. Biol., 28, 909, 10.1038/s41594-021-00676-5

Zhang, 2021, Enzymatic reactions inside biological condensates, J. Mol. Biol., 433, 10.1016/j.jmb.2020.08.009

Zhao, 2020, Phase separation in membrane biology: the interplay between membrane-bound organelles and membraneless condensates, Dev. Cell, 55, 30, 10.1016/j.devcel.2020.06.033

Zhou, 2018, Why do disordered and structured proteins behave differently in phase separation?, Trends Biochem. Sci., 43, 499, 10.1016/j.tibs.2018.03.007

Zihni, 2016, Tight junctions: from simple barriers to multifunctional molecular gates, Nat. Rev. Mol. Cell Biol., 17, 564, 10.1038/nrm.2016.80