Navigating Membrane Protein Structure, Dynamics, and Energy Landscapes Using Spin Labeling and EPR Spectroscopy

Akyuz, 2013, Transport dynamics in a glutamate transporter homologue, Nature, 502, 114, 10.1038/nature12265 Akyuz, 2015, Transport domain unlocking sets the uptake rate of an aspartate transporter, Nature, 518, 68, 10.1038/nature14158 Alexander, 2008, De novo high-resolution protein structure determination from sparse spin-labeling EPR data, Structure, 16, 181, 10.1016/j.str.2007.11.015 Altenbach, 2005, Accessibility of nitroxide side chains: Absolute Heisenberg exchange rates from power saturation EPR, Biophysical Journal, 89, 2103, 10.1529/biophysj.105.059063 Altenbach, 1994, A collision gradient method to determine the immersion depth of nitroxides in lipid bilayers: Application to spin-labeled mutants of bacteriorhodopsin, Proceedings of the National Academy of Sciences of the United States of America, 91, 1667, 10.1073/pnas.91.5.1667 Altenbach, 2008, High-resolution distance mapping in rhodopsin reveals the pattern of helix movement due to activation, Proceedings of the National Academy of Sciences of the United States of America, 105, 7439, 10.1073/pnas.0802515105 Altenbach, 1990, Transmembrane protein structure: Spin labeling of bacteriorhodopsin mutants, Science, 248, 1088, 10.1126/science.2160734 Bayburt, 2010, Membrane protein assembly into Nanodiscs, FEBS Letters, 584, 1721, 10.1016/j.febslet.2009.10.024 Berliner, 1982, A novel reversible thiol-specific spin label: Papain active site labeling and inhibition, Analytical Biochemistry, 119, 450, 10.1016/0003-2697(82)90612-1 Bhabha, 2013, Divergent evolution of protein conformational dynamics in dihydrofolate reductase, Nature Structural & Molecular Biology, 20, 1243, 10.1038/nsmb.2676 Bhattacharjee, 2011, Site-specific radical formation in DNA induced by Cu(II)-H(2)O(2) oxidizing system, using ESR, immuno-spin trapping, LC-MS, and MS/MS, Free Radical Biology & Medicine, 50, 1536, 10.1016/j.freeradbiomed.2011.02.034 Borbat, 2002, Protein structure determination using long-distance constraints from double-quantum coherence ESR: Study of T4 lysozyme, Journal of the American Chemical Society, 124, 5304, 10.1021/ja020040y Borbat, 2007, Conformational motion of the ABC transporter MsbA induced by ATP hydrolysis, PLoS Biology, 5, 10.1371/journal.pbio.0050271 Brandon, 2012, The global analysis of DEER data, Journal of Magnetic Resonance, 218, 93, 10.1016/j.jmr.2012.03.006 Britt, 2004, Recent pulsed EPR studies of the photosystem II oxygen-evolving complex: Implications as to water oxidation mechanisms, Biochimica et Biophysica Acta, 1655, 158, 10.1016/j.bbabio.2003.11.009 Brunger, 2011, Three-dimensional molecular modeling with single molecule FRET, Journal of Structural Biology, 173, 497, 10.1016/j.jsb.2010.09.004 Calvo, 1990, Electron paramagnetic resonance investigation of photosynthetic reaction centers from Rhodobacter sphaeroides R-26 in which Fe2+ was replaced by Cu2+. Determination of hyperfine interactions and exchange and dipole-dipole interactions between Cu2+ and QA, Biophysical Journal, 58, 149, 10.1016/S0006-3495(90)82361-4 Chiang, 2005, The determination of pair distance distributions by pulsed ESR using Tikhonov regularization, Journal of Magnetic Resonance, 172, 279, 10.1016/j.jmr.2004.10.012 Choe, 2011, Crystal structure of metarhodopsin II, Nature, 471, 651, 10.1038/nature09789 Claxton, 2010, Ion/substrate-dependent conformational dynamics of a bacterial homolog of neurotransmitter:sodium symporters, Nature Structural & Molecular Biology, 17, 822, 10.1038/nsmb.1854 Columbus, 2002, A new spin on protein dynamics, Trends in Biochemical Sciences, 27, 288, 10.1016/S0968-0004(02)02095-9 Columbus, 2001, Molecular motion of spin labeled side chains in alpha-helices: Analysis by variation of side chain structure, Biochemistry, 40, 3828, 10.1021/bi002645h Cordero-Morales, 2007, Molecular driving forces determining potassium channel slow inactivation, Nature Structural & Molecular Biology, 14, 1062, 10.1038/nsmb1309 Cortes, 2001, Molecular architecture of full-length KcsA: Role of cytoplasmic domains in ion permeation and activation gating, The Journal of General Physiology, 117, 165, 10.1085/jgp.117.2.165 Cross, 2011, Influence of solubilizing environments on membrane protein structures, Trends in Biochemical Sciences, 36, 117, 10.1016/j.tibs.2010.07.005 Cuello, 2004, Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid bilayer, Science, 306, 491, 10.1126/science.1101373 Cuello, 2010, Structural basis for the coupling between activation and inactivation gates in K(+) channels, Nature, 466, 272, 10.1038/nature09136 Dong, 2005, Structural basis of energy transduction in the transport cycle of MsbA, Science, 308, 1023, 10.1126/science.1106592 Durr, 2014, Structure and dynamics of AMPA receptor GluA2 in resting, pre-open, and desensitized states, Cell, 158, 778, 10.1016/j.cell.2014.07.023 Faham, 2008, The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport, Science, 321, 810, 10.1126/science.1160406 Fajer, 2007, Practical pulsed dipolar ESR (DEER), Vol. 27, 95, 10.1007/978-0-387-49367-1_4 Fanucci, 2003, Substrate-induced conformational changes of the periplasmic N-terminus of an outer-membrane transporter by site-directed spin labeling, Biochemistry, 42, 1391, 10.1021/bi027120z Fanucci, 2003, Spectroscopic evidence that osmolytes used in crystallization buffers inhibit a conformation change in a membrane protein, Biochemistry, 42, 13106, 10.1021/bi035439t Forrest, 2011, The structural basis of secondary active transport mechanisms, Biochimica et Biophysica Acta, 1807, 167, 10.1016/j.bbabio.2010.10.014 Fraser, 1971, Barriers to rotation about the sulfur-sulfur bond in acyclic disulfides, Journal of the American Chemical Society, 93, 3822, 10.1021/ja00744a075 Freed, 2010, Conformational exchange in a membrane transport protein is altered in protein crystals, Biophysical Journal, 99, 1604, 10.1016/j.bpj.2010.06.026 Freed, 2013, Monomeric TonB and the Ton box are required for the formation of a high-affinity transporter-TonB complex, Biochemistry, 52, 2638, 10.1021/bi3016108 Georgieva, 2013, Conformational ensemble of the sodium-coupled aspartate transporter, Nature Structural & Molecular Biology, 20, 215, 10.1038/nsmb.2494 Ghimire, 2009, Significantly improved sensitivity of Q-band PELDOR/DEER experiments relative to X-band is observed in measuring the intercoil distance of a leucine zipper motif peptide (GCN4-LZ), Biochemistry, 48, 5782, 10.1021/bi900781u Griffin, 2011, Antibody fragments as tools in crystallography, Clinical and Experimental Immunology, 165, 285, 10.1111/j.1365-2249.2011.04427.x Hanelt, 2013, Conformational heterogeneity of the aspartate transporter Glt(Ph), Nature Structural & Molecular Biology, 20, 210, 10.1038/nsmb.2471 Hilger, 2005, Assessing oligomerization of membrane proteins by four-pulse DEER: pH-dependent dimerization of NhaA Na+/H+ antiporter of E. coli, Biophysical Journal, 89, 1328, 10.1529/biophysj.105.062232 Hirst, 2011, RosettaEPR: An integrated tool for protein structure determination from sparse EPR data, Journal of Structural Biology, 173, 506, 10.1016/j.jsb.2010.10.013 Hubbell, 1994, Investigation of structure and dynamics in membrane proteins using site-directed spin labeling, Current Opinion in Structural Biology, 4, 566, 10.1016/S0959-440X(94)90219-4 Hubbell, 2003, Rhodopsin structure, dynamics, and activation: A perspective from crystallography, site-directed spin labeling, sulfhydryl reactivity, and disulfide cross-linking, Advances in Protein Chemistry, 63, 243, 10.1016/S0065-3233(03)63010-X Hubbell, 2000, Identifying conformational changes with site-directed spin labeling, Nature Structural Biology, 7, 735, 10.1038/78956 Hubbell, 2013, Technological advances in site-directed spin labeling of proteins, Current Opinion in Structural Biology, 23, 725, 10.1016/j.sbi.2013.06.008 Hubbell, 1996, Watching proteins move using site-directed spin labeling, Structure, 4, 779, 10.1016/S0969-2126(96)00085-8 Hustedt, 2006, Dipolar coupling between nitroxide spin labels: The development and application of a tether-in-a-cone model, Biophysical Journal, 90, 340, 10.1529/biophysj.105.068544 Islam, 2013, Structural refinement from restrained-ensemble simulations based on EPR/DEER data: Application to T4 lysozyme, The Journal of Physical Chemistry. B, 117, 4740, 10.1021/jp311723a Jao, 2008, Structure of membrane-bound alpha-synuclein from site-directed spin labeling and computational refinement, Proceedings of the National Academy of Sciences of the United States of America, 105, 19666, 10.1073/pnas.0807826105 Jeschke, 2006, DeerAnalysis2006—A comprehensive software package for analyzing pulsed ELDOR data, Applied Magnetic Resonance, 30, 473, 10.1007/BF03166213 Jeschke, 2007, Distance measurements on spin-labelled biomacromolecules by pulsed electron paramagnetic resonance, Physical Chemistry Chemical Physics, 9, 1895, 10.1039/b614920k Jeschke, 2004, Interresidual distance determination by four-pulse double electron–electron resonance in an integral membrane protein: The Na+/proline transporter PutP of Escherichia coli, Biophysical Journal, 86, 2551, 10.1016/S0006-3495(04)74310-6 Jiao, 1992, Ab initio molecular orbital studies of the rotational barriers and the sulfur-33 and carbon-13 chemical shieldings for dimethyl disulfide, Journal of the American Chemical Society, 114, 3639, 10.1021/ja00036a010 Kazmier, 2011, Algorithm for selection of optimized EPR distance restraints for de novo protein structure determination, Journal of Structural Biology, 173, 549, 10.1016/j.jsb.2010.11.003 Kazmier, 2014, Conformational cycle and ion-coupling mechanism of the Na+/hydantoin transporter Mhp1, Proceedings of the National Academy of Sciences of the United States of America, 111, 14752, 10.1073/pnas.1410431111 Kazmier, 2014, Conformational dynamics of ligand-dependent alternating access in LeuT, Nature Structural & Molecular Biology, 21, 472, 10.1038/nsmb.2816 Khelashvili, 2013, The membrane protein LeuT in micellar systems: Aggregation dynamics and detergent binding to the S2 site, Journal of the American Chemical Society, 135, 14266, 10.1021/ja405984v Klare, 2013, Site-directed spin labeling EPR spectroscopy in protein research, Biological Chemistry, 394, 1281, 10.1515/hsz-2013-0155 Klare, 2009, Spin labeling EPR, Photosynthesis Research, 102, 377, 10.1007/s11120-009-9490-7 Krishnamurthy, 2012, X-ray structures of LeuT in substrate-free outward-open and apo inward-open states, Nature, 481, 469, 10.1038/nature10737 Krishnamurthy, 2009, Unlocking the molecular secrets of sodium-coupled transporters, Nature, 459, 347, 10.1038/nature08143 Kroncke, 2010, Structural origins of nitroxide side chain dynamics on membrane protein alpha-helical sites, Biochemistry, 49, 10045, 10.1021/bi101148w Langen, 2000, Crystal structures of spin labeled T4 lysozyme mutants: Implications for the interpretation of EPR spectra in terms of structure, Biochemistry, 39, 8396, 10.1021/bi000604f Levitt, 2007, Growth of novel protein structural data, Proceedings of the National Academy of Sciences of the United States of America, 104, 3183, 10.1073/pnas.0611678104 Lin, 2015, SLC transporters as therapeutic targets: Emerging opportunities, Nature Reviews. Drug Discovery, 14, 543, 10.1038/nrd4626 Ma, 2012, Structure and mechanism of a glutamate-GABA antiporter, Nature, 483, 632, 10.1038/nature10917 Masureel, 2014, Protonation drives the conformational switch in the multidrug transporter LmrP, Nature Chemical Biology, 10, 149, 10.1038/nchembio.1408 Mchaourab, 1999, Motion of spin-labeled side chains in T4 lysozyme: Effect of side chain structure, Biochemistry, 38, 2947, 10.1021/bi9826310 Mchaourab, 1996, Motion of spin-labeled side chains in T4 lysozyme. Correlation with protein structure and dynamics, Biochemistry, 35, 7692, 10.1021/bi960482k McHaourab, 1997, Conformation of T4 lysozyme in solution. Hinge-bending motion and the substrate-induced conformational transition studied by site-directed spin labeling, Biochemistry, 36, 307, 10.1021/bi962114m McHaourab, 2011, Toward the fourth dimension of membrane protein structure: Insight into dynamics from spin-labeling EPR spectroscopy, Structure, 19, 1549, 10.1016/j.str.2011.10.009 Meyer, 2015, Room-temperature distance measurements of immobilized spin-labeled protein by DEER/PELDOR, Biophysical Journal, 108, 1213, 10.1016/j.bpj.2015.01.015 Mishra, 2014, Conformational dynamics of the nucleotide binding domains and the power stroke of a heterodimeric ABC transporter, eLife, 3, 10.7554/eLife.02740 Mittermaier, 2009, Observing biological dynamics at atomic resolution using NMR, Trends in Biochemical Sciences, 34, 601, 10.1016/j.tibs.2009.07.004 Nigam, 2015, What do drug transporters really do?, Nature Reviews. Drug Discovery, 14, 29, 10.1038/nrd4461 Overington, 2006, How many drug targets are there?, Nature Reviews. Drug Discovery, 5, 993, 10.1038/nrd2199 Palczewski, 2000, Crystal structure of rhodopsin: A G protein-coupled receptor, Science, 289, 739, 10.1126/science.289.5480.739 Pannier, 2000, Dead-time free measurement of dipole-dipole interactions between electron spins, Journal of Magnetic Resonance, 142, 331, 10.1006/jmre.1999.1944 Pardon, 2014, A general protocol for the generation of nanobodies for structural biology, Nature Protocols, 9, 674, 10.1038/nprot.2014.039 Penmatsa, 2013, X-ray structure of dopamine transporter elucidates antidepressant mechanism, Nature, 503, 85, 10.1038/nature12533 Perez, 2012, Alternating-access mechanism in conformationally asymmetric trimers of the betaine transporter BetP, Nature, 490, 126, 10.1038/nature11403 Perozo, 1999, Structural rearrangements underlying K+-channel activation gating, Science, 285, 73, 10.1126/science.285.5424.73 Perozo, 2002, Open channel structure of MscL and the gating mechanism of mechanosensitive channels, Nature, 418, 942, 10.1038/nature00992 Polyhach, 2011, Rotamer libraries of spin labelled cysteines for protein studies, Physical Chemistry Chemical Physics, 13, 2356, 10.1039/C0CP01865A Quick, 2012, Experimental conditions can obscure the second high-affinity site in LeuT, Nature Structural & Molecular Biology, 19, 207, 10.1038/nsmb.2197 Quick, 2009, Binding of an octylglucoside detergent molecule in the second substrate (S2) site of LeuT establishes an inhibitor-bound conformation, Proceedings of the National Academy of Sciences of the United States of America, 106, 5563, 10.1073/pnas.0811322106 Rabenstein, 1995, Determination of the distance between two spin labels attached to a macromolecule, Proceedings of the National Academy of Sciences of the United States of America, 92, 8239, 10.1073/pnas.92.18.8239 Roux, 2013, Restrained-ensemble molecular dynamics simulations based on distance histograms from double electron–electron resonance spectroscopy, The Journal of Physical Chemistry. B, 117, 4733, 10.1021/jp3110369 Roy, 2015, Membrane preparation and solubilization, Methods in Enzymology, 557, 45, 10.1016/bs.mie.2014.11.044 Salom, 2006, Crystal structure of a photoactivated deprotonated intermediate of rhodopsin, Proceedings of the National Academy of Sciences of the United States of America, 103, 16123, 10.1073/pnas.0608022103 Serrano-Vega, 2008, Conformational thermostabilization of the beta1-adrenergic receptor in a detergent-resistant form, Proceedings of the National Academy of Sciences of the United States of America, 105, 877, 10.1073/pnas.0711253105 Shimamura, 2010, Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1, Science, 328, 470, 10.1126/science.1186303 Sillitoe, 2015, CATH: Comprehensive structural and functional annotations for genome sequences, Nucleic Acids Research, 43, D376, 10.1093/nar/gku947 Sonoda, 2011, Benchmarking membrane protein detergent stability for improving throughput of high-resolution X-ray structures, Structure, 19, 17, 10.1016/j.str.2010.12.001 Subczynski, 2011, Spin-label oximetry at Q- and W-band, Journal of Magnetic Resonance, 209, 142, 10.1016/j.jmr.2011.01.003 ter Beek, 2014, Structural diversity of ABC transporters, The Journal of General Physiology, 143, 419, 10.1085/jgp.201411164 Vasquez, 2008, A structural mechanism for MscS gating in lipid bilayers, Science, 321, 1210, 10.1126/science.1159674 Weil, 2007 Wen, 2013, On the origin of large flexibility of P-glycoprotein in the inward-facing state, The Journal of Biological Chemistry, 288, 19211, 10.1074/jbc.M113.450114 Weyand, 2008, Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter, Science, 322, 709, 10.1126/science.1164440 Wiener, 2004, A pedestrian guide to membrane protein crystallization, Methods, 34, 364, 10.1016/j.ymeth.2004.03.025 Xu, 2006, Substrate-dependent unfolding of the energy coupling motif of a membrane transport protein determined by double electron–electron resonance, Biochemistry, 45, 10847, 10.1021/bi061051x Yamashita, 2005, Crystal structure of a bacterial homologue of Na+/Cl−-dependent neurotransmitter transporters, Nature, 437, 215, 10.1038/nature03978 Yang, 2012, Pulsed ESR dipolar spectroscopy for distance measurements in immobilized spin labeled proteins in liquid solution, Journal of the American Chemical Society, 134, 9950, 10.1021/ja303791p Yildirim, 2007, Drug-target network, Nature Biotechnology, 25, 1119, 10.1038/nbt1338 Zhao, 2011, Substrate-modulated gating dynamics in a Na+-coupled neurotransmitter transporter homologue, Nature, 474, 109, 10.1038/nature09971 Zhao, 2010, Single-molecule dynamics of gating in a neurotransmitter transporter homologue, Nature, 465, 188, 10.1038/nature09057 Zhu, 2007, Topology of transmembrane proteins by scanning cysteine accessibility mutagenesis methodology, Methods, 41, 439, 10.1016/j.ymeth.2006.08.004 Zielonka, 2014, High-throughput assays for superoxide and hydrogen peroxide: Design of a screening workflow to identify inhibitors of NADPH oxidases, The Journal of Biological Chemistry, 289, 16176, 10.1074/jbc.M114.548693 Zou, 2009, Conformational cycle of the ABC transporter MsbA in liposomes: Detailed analysis using double electron–electron resonance spectroscopy, Journal of Molecular Biology, 393, 586, 10.1016/j.jmb.2009.08.050 Zou, 2009, Alternating access of the putative substrate-binding chamber in the ABC transporter MsbA, Journal of Molecular Biology, 393, 574, 10.1016/j.jmb.2009.08.051 Zou, 2010, Increased sensitivity and extended range of distance measurements in spin-labeled membrane proteins: Q-band double electron–electron resonance and nanoscale bilayers, Biophysical Journal, 98, L18, 10.1016/j.bpj.2009.12.4193