Native mass spectrometry and gas-phase fragmentation provide rapid and in-depth topological characterization of a PROTAC ternary complex

Allison, 2019, Structural mass spectrometry comes of new age: new insight into protein structure, function and interactions, Biochem. Soc. Trans., 47, 317, 10.1042/BST20180356 Beveridge, 2020, Native mass spectrometry can effectively predict PROTAC efficacy, ACS Cent. Sci., 6, 1223, 10.1021/acscentsci.0c00049 Beveridge, 2019, Ion mobility mass spectrometry uncovers the impact of the patterning of oppositely charged residues on the conformational distributions of intrinsically disordered proteins, J. Am. Chem. Soc., 141, 4908, 10.1021/jacs.8b13483 Boeri Erba, 2020, Exploring the structure and dynamics of macromolecular complexes by native mass spectrometry, J. Proteomics, 222, 103799, 10.1016/j.jprot.2020.103799 Bondeson, 2015, Catalytic in vivo protein knockdown by small-molecule PROTACs, Nat. Chem. Biol., 11, 611, 10.1038/nchembio.1858 Bondeson, 2018, Lessons in PROTAC design from selective degradation with a promiscuous warhead, Cell Chem. Biol., 25, 78, 10.1016/j.chembiol.2017.09.010 Bornschein, 2016, Ion mobility-mass spectrometry reveals highly-compact intermediates in the collision induced dissociation of charge-reduced protein complexes, J. Am. Soc. Mass Spectrom., 27, 41, 10.1007/s13361-015-1250-7 Breuker, 2008, Stepwise evolution of protein native structure with electrospray into the gas phase, 10(-12) to 10(2) s, Proc. Natl. Acad. Sci. U S A, 105, 18145, 10.1073/pnas.0807005105 Brodbelt, 2014, Photodissociation mass spectrometry: new tools for characterization of biological molecules, Chem. Soc. Rev., 43, 2757, 10.1039/C3CS60444F Brodbelt, 2020, Ultraviolet photodissociation mass spectrometry for analysis of biological molecules, Chem. Rev., 120, 3328, 10.1021/acs.chemrev.9b00440 Bush, 2010, Collision cross sections of proteins and their complexes: a calibration framework and database for gas-phase structural biology, Anal. Chem., 82, 9557, 10.1021/ac1022953 Catalina, 2005, Decharging of globular proteins and protein complexes in electrospray, Chemistry (Easton), 11, 960 Collins, 2017, Chemical approaches to targeted protein degradation through modulation of the ubiquitin-proteasome pathway, Biochem. J., 474, 1127, 10.1042/BCJ20160762 Cui, 2015, Electron-capture dissociation and ion mobility mass spectrometry for characterization of the hemoglobin protein assembly, Protein Sci., 24, 1325, 10.1002/pro.2712 Dixit, 2018, Collision induced unfolding of isolated proteins in the gas phase: past, present, and future, Curr. Opin. Chem. Biol., 42, 93, 10.1016/j.cbpa.2017.11.010 Edmondson, 2019, Proteolysis targeting chimeras (PROTACs) in 'beyond rule-of-five' chemical space: recent progress and future challenges, Bioorg. Med. Chem. Lett., 29, 1555, 10.1016/j.bmcl.2019.04.030 Eschweiler, 2017, Chemical probes and engineered constructs reveal a detailed unfolding mechanism for a solvent-free multidomain protein, J. Am. Chem. Soc., 139, 534, 10.1021/jacs.6b11678 Farnaby, 2019, BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design, Nat. Chem. Biol., 15, 672, 10.1038/s41589-019-0294-6 Gadd, 2017, Structural basis of PROTAC cooperative recognition for selective protein degradation, Nat. Chem. Biol., 13, 514, 10.1038/nchembio.2329 Galdeano, 2014, Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von Hippel-Lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities, J. Med. Chem., 57, 8657, 10.1021/jm5011258 Gault, 2020, Combining native and 'omics' mass spectrometry to identify endogenous ligands bound to membrane proteins, Nat. Methods, 17, 505, 10.1038/s41592-020-0821-0 Hall, 2012, Structural modeling of heteromeric protein complexes from disassembly pathways and ion mobility-mass spectrometry, Structure, 20, 1596, 10.1016/j.str.2012.07.001 Heck, 2008, Native mass spectrometry: a bridge between interactomics and structural biology, Nat. Methods, 5, 927, 10.1038/nmeth.1265 Hogan, 2009, Combined charged residue-field emission model of macromolecular electrospray ionization, Anal. Chem., 81, 369, 10.1021/ac8016532 Horn, 2000, Activated ion electron capture dissociation for mass spectral sequencing of larger (42 kDa) proteins, Anal. Chem., 72, 4778, 10.1021/ac000494i Jurchen, 2003, Origin of asymmetric charge partitioning in the dissociation of gas-phase protein homodimers, J. Am. Chem. Soc., 125, 2817, 10.1021/ja0211508 Khristenko, 2019, Native ion mobility mass spectrometry: when gas-phase ion structures depend on the electrospray charging process, J. Am. Soc. Mass Spectrom., 30, 1069, 10.1007/s13361-019-02152-3 Konermann, 2009, A simple model for the disintegration of highly charged solvent droplets during electrospray ionization, J. Am. Soc. Mass Spectrom., 20, 496, 10.1016/j.jasms.2008.11.007 Laganowsky, 2013, Mass spectrometry of intact membrane protein complexes, Nat. Protoc., 8, 639, 10.1038/nprot.2013.024 Lemaire, 2001, Stabilization of gas-phase noncovalent macromolecular complexes in electrospray mass spectrometry using aqueous triethylammonium bicarbonate buffer, Anal. Chem., 73, 1699, 10.1021/ac001276s Lermyte, 2018, Radical solutions: principles and application of electron-based dissociation in mass spectrometry-based analysis of protein structure, Mass Spectrom. Rev., 37, 750, 10.1002/mas.21560 Li, 2020, Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy, J. Hematol. Oncol., 13, 50, 10.1186/s13045-020-00885-3 Loo, 2016, Salt bridge rearrangement (SaBRe) explains the dissociation behavior of noncovalent complexes, J. Am. Soc. Mass Spectrom., 27, 975, 10.1007/s13361-016-1375-3 McAllister, 2015, Release of native-like gaseous proteins from electrospray droplets via the charged residue mechanism: insights from molecular dynamics simulations, J. Am. Chem. Soc., 137, 12667, 10.1021/jacs.5b07913 Mehmood, 2014, Charge reduction stabilizes intact membrane protein complexes for mass spectrometry, J. Am. Chem. Soc., 136, 17010, 10.1021/ja510283g Nallamsetty, 2004, Efficient site-specific processing of fusion proteins by tobacco vein mottling virus protease in vivo and in vitro, Protein Expr. Purif., 38, 108, 10.1016/j.pep.2004.08.016 Ottis, 2017, Proteolysis-targeting chimeras: induced protein degradation as a therapeutic strategy, ACS Chem. Biol., 12, 892, 10.1021/acschembio.6b01068 Pacholarz, 2016, Use of a charge reducing agent to enable intact mass analysis of cysteine-linked antibody-drug-conjugates by native mass spectrometry, EuPA Open Proteom., 11, 23, 10.1016/j.euprot.2016.02.004 Pagel, 2010, Alternate dissociation pathways identified in charge-reduced protein complex ions, Anal. Chem., 82, 5363, 10.1021/ac101121r Pettersson, 2019, PROteolysis TArgeting Chimeras (PROTACs)—past, present and future, Drug Discov. Today Technol., 31, 15, 10.1016/j.ddtec.2019.01.002 Polasky, 2019, CIUSuite 2: next-generation software for the analysis of gas-phase protein unfolding data, Anal. Chem., 91, 3147, 10.1021/acs.analchem.8b05762 Popa, 2016, Collision-induced dissociation of electrosprayed protein complexes: an all-atom molecular dynamics model with mobile protons, J. Phys. Chem. B, 120, 5114, 10.1021/acs.jpcb.6b03035 Pukala, 2009, Subunit architecture of multiprotein assemblies determined using restraints from gas-phase measurements, Structure, 17, 1235, 10.1016/j.str.2009.07.013 Roy, 2019, SPR-measured dissociation kinetics of PROTAC ternary complexes influence target degradation rate, ACS Chem. Biol., 14, 361, 10.1021/acschembio.9b00092 Ruotolo, 2008, Ion mobility-mass spectrometry analysis of large protein complexes, Nat. Protoc., 3, 1139, 10.1038/nprot.2008.78 Sternicki, 2021, Native mass spectrometry for the study of PROTAC GNE-987-containing ternary complexes, Chem. Med. Chem., 16, 1, 10.1002/cmdc.202100113 Wang, 2020, Releasing nonperipheral subunits from protein complexes in the gas phase, Anal. Chem., 92, 15799, 10.1021/acs.analchem.0c02845 Wang, 2019, Native mass spectrometry, ion mobility, electron-capture dissociation, and modeling provide structural information for gas-phase apolipoprotein E oligomers, J. Am. Soc. Mass Spectrom., 30, 876, 10.1007/s13361-019-02148-z Wells, 2005, Collision-induced dissociation (CID) of peptides and proteins, Methods Enzymol., 402, 148, 10.1016/S0076-6879(05)02005-7 Xie, 2006, Top-down ESI-ECD-FT-ICR mass spectrometry localizes noncovalent protein-ligand binding sites, J. Am. Chem. Soc., 128, 14432, 10.1021/ja063197p Yan, 2017, Surface-induced dissociation of protein complexes in a hybrid Fourier transform ion cyclotron resonance mass spectrometer, Anal. Chem., 89, 895, 10.1021/acs.analchem.6b03986 Zengerle, 2015, Selective small molecule induced degradation of the BET bromodomain protein BRD4, ACS Chem. Biol., 10, 1770, 10.1021/acschembio.5b00216 Zhang, 2011, Native electrospray and electron-capture dissociation FTICR mass spectrometry for top-down studies of protein assemblies, Anal. Chem., 83, 5598, 10.1021/ac200695d Zhurov, 2013, Principles of electron capture and transfer dissociation mass spectrometry applied to peptide and protein structure analysis, Chem. Soc. Rev., 42, 5014, 10.1039/c3cs35477f Zorba, 2018, Delineating the role of cooperativity in the design of potent PROTACs for BTK, Proc. Natl. Acad. Sci. U S A, 115, E7285, 10.1073/pnas.1803662115