Tracking Higher Order Protein Structure by Hydrogen-Deuterium Exchange Mass Spectrometry

Author(s): Mark Benhaim, Kelly K. Lee, Miklos Guttman*.

Journal Name: Protein & Peptide Letters

Volume 26 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Structural biology has provided a fundamental understanding of protein structure and mechanistic insight into their function. However, high-resolution structures alone are insufficient for a complete understanding of protein behavior. Higher energy conformations, conformational changes, and subtle structural fluctuations that underlie the proper function of proteins are often difficult to probe using traditional structural approaches. Hydrogen/Deuterium Exchange with Mass Spectrometry (HDX-MS) provides a way to probe the accessibility of backbone amide protons under native conditions, which reports on local structural dynamics of solution protein structure that can be used to track complex structural rearrangements that occur in the course of a protein’s function.

Conclusion: In the last 20 years the advances in labeling techniques, sample preparation, instrumentation, and data analysis have enabled HDX to gain insights into very complex biological systems. Analysis of challenging targets such as membrane protein complexes is now feasible and the field is paving the way to the analysis of more and more complex systems.

Keywords: Hydrogen deuterium exchange, footprinting, protein structure, protein dynamics, structural mass spectrometry, pulse labeling.

Englander, S.W. Hydrogen exchange and mass spectrometry: A historical perspective. J. Am. Soc. Mass Spectrom., 2006, 17(11), 1481-1489.
Wang, G.; Abzalimov, R.R.; Bobst, C.E.; Kaltashov, I.A. Conformer-specific characterization of nonnative protein states using hydrogen exchange and top-down mass spectrometry. Proc. Natl. Acad. Sci. USA, 2013, 110(50), 20087-20092.
Mandell, J.G.; Baerga-Ortiz, A.; Falick, A.M.; Komives, E.A. Measurement of solvent accessibility at protein-protein interfaces. Methods Mol. Biol., 2005, 305, 65-80.
Marcsisin, S.R.; Engen, J.R. Hydrogen exchange mass spectrometry: What is it and what can it tell us? Anal. Bioanal. Chem., 2010, 397(3), 967-972.
Marciano, D.P.; Dharmarajan, V.; Griffin, P.R. HDX-MS guided drug discovery: Small molecules and biopharmaceuticals. Curr. Opin. Struct. Biol., 2014, 28, 105-111.
Maaty, W.S.; Weis, D.D. Label-Free, in-solution screening of peptide libraries for binding to protein targets using hydrogen exchange mass spectrometry. J. Am. Chem. Soc., 2016, 138(4), 1335-1343.
Pantazatos, D.; Kim, J.S.; Klock, H.E.; Stevens, R.C.; Wilson, I.A.; Lesley, S.A.; Woods, V.L. Jr. Rapid refinement of crystallographic protein construct definition employing enhanced hydrogen/deuterium exchange MS. Proc. Natl. Acad. Sci. USA, 2004, 101(3), 751-756.
Fowler, M.L.; McPhail, J.A.; Jenkins, M.L.; Masson, G.R.; Rutaganira, F.U.; Shokat, K.M.; Williams, R.L.; Burke, J.E. Using hydrogen deuterium exchange mass spectrometry to engineer optimized constructs for crystallization of protein complexes: Case study of PI4KIIIbeta with Rab11. Protein Sci., 2016, 25(4), 826-839.
Tu, T.; Dragusanu, M.; Petre, B.A.; Rempel, D.L.; Przybylski, M.; Gross, M.L. Protein-peptide affinity determination using an h/d exchange dilution strategy: Application to antigen-antibody interactions. J. Am. Soc. Mass Spectrom., 2010, 21(10), 1660-1667.
Weis, D.D. Hydrogen Exchange Mass Spectrometry of Proteins: Fundamentals, Methods, and Applications; John Wiley & Sons: Hoboken, New Jersey, 2016.
Kazazic, S.; Zhang, H.M.; Schaub, T.M.; Emmett, M.R.; Hendrickson, C.L.; Blakney, G.T.; Marshall, A.G. Automated data reduction for hydrogen/deuterium exchange experiments, enabled by high-resolution fourier transform ion cyclotron resonance mass spectrometry. J. Am. Soc. Mass Spectrom., 2010, 21(4), 550-558.
Iacob, R.E.; Murphy, J.P., III; Engen, J.R. Ion mobility adds an additional dimension to mass spectrometric analysis of solution-phase hydrogen/deuterium exchange. Rapid Commun. Mass Spectrom., 2008, 22(18), 2898-2904.
Harrison, R.A.; Engen, J.R. Conformational insight into multi-protein signaling assemblies by hydrogen-deuterium exchange mass spectrometry. Curr. Opin. Struct. Biol., 2016, 41, 187-193.
Shi, Y.; Chen, X.; Elsasser, S.; Stocks, B.B.; Tian, G.; Lee, B.H.; Zhang, N.; de Poot, S.A.; Tuebing, F.; Sun, S.; Vannoy, J.; Tarasov, S.G.; Engen, J.R.; Finley, D.; Walters, K.J. Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome. Science, 2016, 351(6275), aad9421.
Wales, T.E.; Fadgen, K.E.; Gerhardt, G.C.; Engen, J.R. High-speed and high-resolution UPLC separation at zero degrees Celsius. Anal. Chem., 2008, 80(17), 6815-6820.
Venable, J.D.; Okach, L.; Agarwalla, S.; Brock, A. Subzero temperature chromatography for reduced back-exchange and improved dynamic range in amide hydrogen/deuterium exchange mass spectrometry. Anal. Chem., 2012, 84(21), 9601-9608.
Valeja, S.G.; Emmett, M.R.; Marshall, A.G. Polar aprotic modifiers for chromatographic separation and back-exchange reduction for protein hydrogen/deuterium exchange monitored by fourier transform ion cyclotron resonance mass spectrometry. J. Am. Soc. Mass Spectrom., 2012, 23(4), 699-707.
Black, W.A.; Stocks, B.B.; Mellors, J.S.; Engen, J.R.; Ramsey, J.M. Utilizing microchip capillary electrophoresis electrospray ionization for hydrogen exchange mass spectrometry. Anal. Chem., 2015, 87(12), 6280-6287.
Yan, X.; Zhang, H.; Watson, J.; Schimerlik, M.I.; Deinzer, M.L. Hydrogen/deuterium exchange and mass spectrometric analysis of a protein containing multiple disulfide bonds: Solution structure of recombinant Macrophage Colony Stimulating Factor-beta (rhM-CSFbeta). Protein Sci., 2002, 11(9), 2113-2124.
Koeppe, J.R.; Komives, E.A. Amide H/2H exchange reveals a mechanism of thrombin activation. Biochemistry, 2006, 45(25), 7724-7732.
Burke, J.E.; Karbarz, M.J.; Deems, R.A.; Li, S.; Woods, V.L. Jr.; Dennis, E.A. Interaction of group IA phospholipase A2 with metal ions and phospholipid vesicles probed with deuterium exchange mass spectrometry. Biochemistry, 2008, 47(24), 6451-6459.
Mysling, S.; Salbo, R.; Ploug, M.; Jorgensen, T.J. Electrochemical reduction of disulfide-containing proteins for hydrogen/deuterium exchange monitored by mass spectrometry. Anal. Chem., 2014, 86(1), 340-345.
Trabjerg, E.; Jakobsen, R.U.; Mysling, S.; Christensen, S.; Jorgensen, T.J.; Rand, K.D. Conformational analysis of large and highly disulfide-stabilized proteins by integrating online electrochemical reduction into an optimized H/D exchange mass spectrometry workflow. Anal. Chem., 2015, 87(17), 8880-8888.
Vadas, O.; Jenkins, M.L.; Dornan, G.L.; Burke, J.E. Using hydrogen-deuterium exchange mass spectrometry to examine protein-membrane interactions. Methods Enzymol., 2017, 583, 143-172.
Rey, M.; Mrazek, H.; Pompach, P.; Novak, P.; Pelosi, L.; Brandolin, G.; Forest, E.; Havlicek, V.; Man, P. Effective removal of nonionic detergents in protein mass spectrometry, hydrogen/deuterium exchange, and proteomics. Anal. Chem., 2010, 82(12), 5107-5116.
Zhang, X.; Chien, E.Y.; Chalmers, M.J.; Pascal, B.D.; Gatchalian, J.; Stevens, R.C.; Griffin, P.R. Dynamics of the beta2-adrenergic G-protein coupled receptor revealed by hydrogen-deuterium exchange. Anal. Chem., 2010, 82(3), 1100-1108.
West, G.M.; Chien, E.Y.; Katritch, V.; Gatchalian, J.; Chalmers, M.J.; Stevens, R.C.; Griffin, P.R. Ligand-dependent perturbation of the conformational ensemble for the GPCR beta2 adrenergic receptor revealed by HDX. Structure, 2011, 19(10), 1424-1432.
Chung, K.Y.; Rasmussen, S.G.; Liu, T.; Li, S.; DeVree, B.T.; Chae, P.S.; Calinski, D.; Kobilka, B.K.; Woods, V.L. Jr.; Sunahara, R.K. Conformational changes in the G protein Gs induced by the beta2 adrenergic receptor. Nature, 2011, 477(7366), 611-615.
Westfield, G.H.; Rasmussen, S.G.; Su, M.; Dutta, S.; DeVree, B.T.; Chung, K.Y.; Calinski, D.; Velez-Ruiz, G.; Oleskie, A.N.; Pardon, E.; Chae, P.S.; Liu, T.; Li, S.; Woods, V.L. Jr.; Steyaert, J.; Kobilka, B.K.; Sunahara, R.K.; Skiniotis, G. Structural flexibility of the G alpha s alpha-helical domain in the beta2-adrenoceptor Gs complex. Proc. Natl. Acad. Sci. USA, 2011, 108(38), 16086-16091.
Duc, N.M.; Du, Y.; Thorsen, T.S.; Lee, S.Y.; Zhang, C.; Kato, H.; Kobilka, B.K.; Chung, K.Y. Effective application of bicelles for conformational analysis of G protein-coupled receptors by hydrogen/deuterium exchange mass spectrometry. J. Am. Soc. Mass Spectrom., 2015, 26(5), 808-817.
Pan, Y.; Brown, L.; Konermann, L. Hydrogen exchange mass spectrometry of bacteriorhodopsin reveals light-induced changes in the structural dynamics of a biomolecular machine. J. Am. Chem. Soc., 2011, 133(50), 20237-20244.
Kim, M.; Sun, Z.Y.; Rand, K.D.; Shi, X.; Song, L.; Cheng, Y.; Fahmy, A.F.; Majumdar, S.; Ofek, G.; Yang, Y.; Kwong, P.D.; Wang, J.H.; Engen, J.R.; Wagner, G.; Reinherz, E.L. Antibody mechanics on a membrane-bound HIV segment essential for GP41-targeted viral neutralization. Nat. Struct. Mol. Biol., 2011, 18(11), 1235-1243.
Vahidi, S.; Bi, Y.; Dunn, S.D.; Konermann, L. Load-dependent destabilization of the gamma-rotor shaft in FOF1 ATP synthase revealed by hydrogen/deuterium-exchange mass spectrometry. Proc. Natl. Acad. Sci. USA, 2016, 113(9), 2412-2417.
Hebling, C.M.; Morgan, C.R.; Stafford, D.W.; Jorgenson, J.W.; Rand, K.D.; Engen, J.R. Conformational analysis of membrane proteins in phospholipid bilayer nanodiscs by hydrogen exchange mass spectrometry. Anal. Chem., 2010, 82(13), 5415-5419.
Morgan, C.R.; Hebling, C.M.; Rand, K.D.; Stafford, D.W.; Jorgenson, J.W.; Engen, J.R. Conformational transitions in the membrane scaffold protein of phospholipid bilayer nanodiscs., 2011.
Parker, C.H.; Morgan, C.R.; Rand, K.D.; Engen, J.R.; Jorgenson, J.W.; Stafford, D.W. A conformational investigation of propeptide binding to the integral membrane protein gamma-glutamyl carboxylase using nanodisc hydrogen exchange mass spectrometry. Biochemistry, 2014, 53(9), 1511-1520.
Treuheit, N.A.; Redhair, M.; Kwon, H.; McClary, W.D.; Guttman, M.; Sumida, J.P.; Atkins, W.M. Membrane interactions, ligand-dependent dynamics, and stability of cytochrome P4503A4 in lipid nanodiscs. Biochemistry, 2016, 55(7), 1058-1069.
Adhikary, S.; Deredge, D.J.; Nagarajan, A.; Forrest, L.R.; Wintrode, P.L.; Singh, S.K. Conformational dynamics of a neurotransmitter: Sodium symporter in a lipid bilayer. Proc. Natl. Acad. Sci. USA, 2017, 114(10), E1786-E1795.
Rey, M.; Forest, E.; Pelosi, L. Exploring the conformational dynamics of the bovine ADP/ATP carrier in mitochondria. Biochemistry, 2012, 51(48), 9727-9735.
Rey, M.; Man, P.; Clemencon, B.; Trezeguet, V.; Brandolin, G.; Forest, E.; Pelosi, L. Conformational dynamics of the bovine mitochondrial ADP/ATP carrier isoform 1 revealed by hydrogen/deuterium exchange coupled to mass spectrometry. J. Biol. Chem., 2010, 285(45), 34981-34990.
Garcia, N.K.; Guttman, M.; Ebner, J.L.; Lee, K.K. Dynamic changes during acid-induced activation of influenza hemagglutinin. Structure, 2015, 23(4), 665-676.
Lim, X.X.; Chandramohan, A.; Lim, X.Y.; Bag, N.; Sharma, K.K.; Wirawan, M.; Wohland, T.; Lok, S.M.; Anand, G.S. Conformational changes in intact dengue virus reveal serotype-specific expansion. Nat. Commun., 2017, 8, 14339.
Coales, S.J.; Tuske, S.J.; Tomasso, J.C.; Hamuro, Y. Epitope mapping by amide hydrogen/deuterium exchange coupled with immobilization of antibody, on-line proteolysis, liquid chromatography and mass spectrometry. Rapid Commun. Mass Spectrom., 2009, 23(5), 639-647.
Chen, E.; Salinas, N.D.; Huang, Y.; Ntumngia, F.; Plasencia, M.D.; Gross, M.L.; Adams, J.H.; Tolia, N.H. Broadly neutralizing epitopes in the plasmodium vivax vaccine candidate duffy binding protein. Proc. Natl. Acad. Sci. USA, 2016, 113(22), 6277-6282.
Guttman, M.; Cupo, A.; Julien, J.P.; Sanders, R.W.; Wilson, I.A.; Moore, J.P.; Lee, K.K. Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV. Env. Nat. Commun., 2015, 6, 6144.
Malito, E.; Faleri, A.; Lo Surdo, P.; Veggi, D.; Maruggi, G.; Grassi, E.; Cartocci, E.; Bertoldi, I.; Genovese, A.; Santini, L.; Romagnoli, G.; Borgogni, E.; Brier, S.; Lo Passo, C.; Domina, M.; Castellino, F.; Felici, F.; van der Veen, S.; Johnson, S.; Lea, S.M.; Tang, C.M.; Pizza, M.; Savino, S.; Norais, N.; Rappuoli, R.; Bottomley, M.J.; Masignani, V. Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen. Proc. Natl. Acad. Sci. USA, 2013, 110(9), 3304-3309.
Domina, M.; Cariccio, V.L.; Benfatto, S.; Venza, M.; Venza, I.; Donnarumma, D.; Bartolini, E.; Borgogni, E.; Bruttini, M.; Santini, L.; Midiri, A.; Galbo, R.; Romeo, L.; Patane, F.; Biondo, C.; Norais, N.; Masignani, V.; Teti, G.; Felici, F.; Beninati, C. Epitope mapping of a monoclonal antibody directed against neisserial heparin binding antigen using next generation sequencing of antigen-specific libraries. PLoS One, 2016, 11(8), e0160702.
Malito, E.; Biancucci, M.; Faleri, A.; Ferlenghi, I.; Scarselli, M.; Maruggi, G.; Lo Surdo, P.; Veggi, D.; Liguori, A.; Santini, L.; Bertoldi, I.; Petracca, R.; Marchi, S.; Romagnoli, G.; Cartocci, E.; Vercellino, I.; Savino, S.; Spraggon, G.; Norais, N.; Pizza, M.; Rappuoli, R.; Masignani, V.; Bottomley, M.J. Structure of the meningococcal vaccine antigen NadA and epitope mapping of a bactericidal antibody. Proc. Natl. Acad. Sci. USA, 2014, 111(48), 17128-17133.
Gribenko, A.V.; Parris, K.; Mosyak, L.; Li, S.; Handke, L.; Hawkins, J.C.; Severina, E.; Matsuka, Y.V.; Anderson, A.S. High Resolution mapping of bactericidal monoclonal antibody binding epitopes on Staphylococcus aureus Antigen MntC. PLoS Pathog., 2016, 12(9), e1005908.
Thornburg, N.J.; Zhang, H.; Bangaru, S.; Sapparapu, G.; Kose, N.; Lampley, R.M.; Bombardi, R.G.; Yu, Y.; Graham, S.; Branchizio, A.; Yoder, S.M.; Rock, M.T.; Creech, C.B.; Edwards, K.M.; Lee, D.; Li, S.; Wilson, I.A.; Garcia-Sastre, A.; Albrecht, R.A.; Crowe, J.E. Jr. H7N9 influenza virus neutralizing antibodies that possess few somatic mutations. J. Clin. Invest., 2016, 126(4), 1482-1494.
Vance, D.J.; Tremblay, J.M.; Rong, Y.; Angalakurthi, S.K.; Volkin, D.B.; Middaugh, C.R.; Weis, D.D.; Shoemaker, C.B.; Mantis, N.J. High-resolution epitope positioning of a large collection of neutralizing and nonneutralizing single-domain antibodies on the enzymatic and binding subunits of ricin toxin. Clin. Vaccine Immunol., 2017, 24(12), e00236-e17.
Yang, D.; Frego, L.; Lasaro, M.; Truncali, K.; Kroe-Barrett, R.; Singh, S. Efficient qualitative and quantitative determination of antigen-induced immune responses. J. Biol. Chem., 2016, 291(31), 16361-16374.
Goswami, D.; Devarakonda, S.; Chalmers, M.J.; Pascal, B.D.; Spiegelman, B.M.; Griffin, P.R. Time window expansion for HDX analysis of an intrinsically disordered protein. J. Am. Soc. Mass Spectrom., 2013, 24(10), 1584-1592.
Hamuro, Y. Determination of Equine Cytochrome c Backbone Amide Hydrogen/Deuterium exchange rates by mass spectrometry using a wider time window and isotope envelope. J. Am. Soc. Mass Spectrom., 2017, 28(3), 486-497.
Guttman, M.; Scian, M.; Lee, K.K. Tracking hydrogen/deuterium exchange at glycan sites in glycoproteins by mass spectrometry. Anal. Chem., 2011, 83(19), 7492-7499.
Huang, R.Y.; Hudgens, J.W. Effects of desialylation on human alpha1-acid glycoprotein-ligand interactions. Biochemistry, 2013, 52(40), 7127-7136.
Jensen, P.F.; Comamala, G.; Trelle, M.B.; Madsen, J.B.; Jorgensen, T.J.; Rand, K.D. Removal of N-Linked glycosylations at acidic pH by PNGase A facilitates hydrogen/deuterium exchange mass spectrometry analysis of N-Linked glycoproteins. Anal. Chem., 2016, 88(24), 12479-12488.
Pan, J.; Zhang, S.; Chou, A.; Hardie, D.B.; Borchers, C.H. Fast comparative structural characterization of intact therapeutic antibodies using hydrogen–deuterium exchange and electron transfer dissociation. Anal. Chem., 2015, 87(12), 5884-5890.
Houde, D.; Berkowitz, S.A.; Engen, J.R. The utility of hydrogen/deuterium exchange mass spectrometry in biopharmaceutical comparability studies. J. Pharm. Sci., 2011, 100(6), 2071-2086.
Houde, D.; Arndt, J.; Domeier, W.; Berkowitz, S.; Engen, J.R. Characterization of IgG1 conformation and conformational dynamics by hydrogen/deuterium exchange mass spectrometry. Anal. Chem., 2009, 81(14), 5966.
Houde, D.; Peng, Y.; Berkowitz, S.A.; Engen, J.R. Post-translational modifications differentially affect IgG1 conformation and receptor binding. Mol. Cell. Proteomics, 2010, 9(8), 1716-1728.
Jensen, P.F.; Larraillet, V.; Schlothauer, T.; Kettenberger, H.; Hilger, M.; Rand, K.D. Investigating the interaction between the neonatal Fc receptor and monoclonal antibody variants by hydrogen/deuterium exchange mass spectrometry. Mol. Cell. Proteomics, 2015, 14(1), 148-161.
Fang, J.; Richardson, J.; Du, Z.; Zhang, Z. Effect of Fc-Glycan structure on the conformational stability of IgG revealed by hydrogen/deuterium exchange and limited proteolysis. Biochemistry, 2016, 55(6), 860-868.
Arora, J.; Hickey, J.M.; Majumdar, R.; Esfandiary, R.; Bishop, S.M.; Samra, H.S.; Middaugh, C.R.; Weis, D.D.; Volkin, D.B. Hydrogen exchange mass spectrometry reveals protein interfaces and distant dynamic coupling effects during the reversible self-association of an IgG1 monoclonal antibody. MAbs, 2015, 7(3), 525-539.
Majumdar, R.; Middaugh, C.R.; Weis, D.D.; Volkin, D.B. Hydrogen-deuterium exchange mass spectrometry as an emerging analytical tool for stabilization and formulation development of therapeutic monoclonal antibodies. J. Pharm. Sci., 2015, 104(2), 327-345.
Arora, J.; Joshi, S.B.; Middaugh, C.R.; Weis, D.D.; Volkin, D.B. Correlating the effects of antimicrobial preservatives on conformational stability, aggregation propensity, and backbone flexibility of an IgG1 monoclonal antibody. J. Pharm. Sci., 2017, 106(6), 1508-1518.
Huang, R.Y.; Iacob, R.E.; Krystek, S.R.; Jin, M.; Wei, H.; Tao, L.; Das, T.K.; Tymiak, A.A.; Engen, J.R.; Chen, G. Characterization of aggregation propensity of a human Fc-fusion protein therapeutic by hydrogen/deuterium exchange mass spectrometry. J. Am. Soc. Mass Spectrom., 2016, 28(5), 795-802.
Leurs, U.; Beck, H.; Bonnington, L.; Lindner, I.; Pol, E.; Rand, K. Mapping the interactions of selective biochemical probes of antibody conformation by hydrogen-deuterium exchange mass spectrometry. Chembiochem: Eur. J. Chem Biol., 2017, 18(11), 1016-1021.
Englander, J.J.; Del Mar, C.; Li, W.; Englander, S.W.; Kim, J.S.; Stranz, D.D.; Hamuro, Y.; Woods, V.L. Jr. Protein structure change studied by hydrogen-deuterium exchange, functional labeling, and mass spectrometry. Proc. Natl. Acad. Sci. USA, 2003, 100(12), 7057-7062.
Zhang, H.M.; Kazazic, S.; Schaub, T.M.; Tipton, J.D.; Emmett, M.R.; Marshall, A.G. Enhanced digestion efficiency, peptide ionization efficiency, and sequence resolution for protein hydrogen/deuterium exchange monitored by Fourier transform ion cyclotron resonance mass spectrometry. Anal. Chem., 2008, 80(23), 9034-9041.
Rey, M.; Man, P.; Brandolin, G.; Forest, E.; Pelosi, L. Recombinant immobilized rhizopuspepsin as a new tool for protein digestion in hydrogen/deuterium exchange mass spectrometry. Rapid Commun. Mass Spectrom., 2009, 23(21), 3431-3438.
Ahn, J.; Cao, M.J.; Yu, Y.Q.; Engen, J.R. Accessing the reproducibility and specificity of pepsin and other aspartic proteases. Biochim. Biophys. Acta, 2013, 1834(6), 1222-1229.
Rey, M.; Yang, M.; Burns, K.M.; Yu, Y.; Lees-Miller, S.P.; Schriemer, D.C. Nepenthesin from monkey cups for hydrogen/deuterium exchange mass spectrometry. Mol. Cell. Proteomics, 2013, 12(2), 464-472.
Yang, M.; Hoeppner, M.; Rey, M.; Kadek, A.; Man, P.; Schriemer, D.C. Recombinant nepenthesin II for hydrogen/deuterium exchange mass spectrometry. Anal. Chem., 2015, 87(13), 6681-6687.
Jones, L.M.; Zhang, H.; Vidavsky, I.; Gross, M.L. Online, high-pressure digestion system for protein characterization by hydrogen/deuterium exchange and mass spectrometry. Anal. Chem., 2010, 82(4), 1171-1174.
Wang, L.; Pan, H.; Smith, D.L. Hydrogen exchange-mass spectrometry: Optimization of digestion conditions. Mol. Cell. Proteomics, 2002, 1(2), 132-138.
Ahn, J.; Jung, M.C.; Wyndham, K.; Yu, Y.Q.; Engen, J.R. Pepsin immobilized on high-strength hybrid particles for continuous flow online digestion at 10,000 psi. Anal. Chem., 2012, 84(16), 7256-7262.
Mayne, L.; Kan, Z.Y.; Chetty, P.S.; Ricciuti, A.; Walters, B.T.; Englander, S.W. Many overlapping peptides for protein hydrogen exchange experiments by the fragment separation-mass spectrometry method. J. Am. Soc. Mass Spectrom., 2011, 22(11), 1898-1905.
Keppel, T.R.; Weis, D.D. Mapping residual structure in intrinsically disordered proteins at residue resolution using millisecond hydrogen/deuterium exchange and residue averaging. J. Am. Soc. Mass Spectrom., 2015, 26(4), 547-554.
Zhang, Z.; Zhang, A.; Xiao, G. Improved protein hydrogen/deuterium exchange mass spectrometry platform with fully automated data processing. Anal. Chem., 2012, 84(11), 4942-4949.
Kan, Z.Y.; Mayne, L.; Chetty, P.S.; Englander, S.W. ExMS: Data analysis for HX-MS experiments. J. Am. Soc. Mass Spectrom., 2011, 22(11), 1906-1915.
Sheff, J.G.; Rey, M.; Schriemer, D.C. Peptide-column interactions and their influence on back exchange rates in hydrogen/deuterium exchange-MS. J. Am. Soc. Mass Spectrom., 2013, 24(7), 1006-1015.
Jorgensen, T.J.; Gardsvoll, H.; Ploug, M.; Roepstorff, P. Intramolecular migration of amide hydrogens in protonated peptides upon collisional activation. J. Am. Chem. Soc., 2005, 127(8), 2785-2793.
Zubarev, R.A.; Horn, D.M.; Fridriksson, E.K.; Kelleher, N.L.; Kruger, N.A.; Lewis, M.A.; Carpenter, B.K.; McLafferty, F.W. Electron capture dissociation for structural characterization of multiply charged protein cations. Anal. Chem., 2000, 72(3), 563-573.
Syka, J.E.; Coon, J.J.; Schroeder, M.J.; Shabanowitz, J.; Hunt, D.F. Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc. Natl. Acad. Sci. USA, 2004, 101(26), 9528-9533.
Rand, K.D.; Adams, C.M.; Zubarev, R.A.; Jorgensen, T.J. Electron capture dissociation proceeds with a low degree of intramolecular migration of peptide amide hydrogens. J. Am. Chem. Soc., 2008, 130(4), 1341-1349.
Rand, K.D.; Zehl, M.; Jensen, O.N.; Jorgensen, T.J. Protein hydrogen exchange measured at single-residue resolution by electron transfer dissociation mass spectrometry. Anal. Chem., 2009, 81(14), 5577-5584.
Zehl, M.; Rand, K.D.; Jensen, O.N.; Jorgensen, T.J. Electron transfer dissociation facilitates the measurement of deuterium incorporation into selectively labeled peptides with single residue resolution. J. Am. Chem. Soc., 2008, 130(51), 17453-17459.
Huang, R.Y.; Garai, K.; Frieden, C.; Gross, M.L. Hydrogen/deuterium exchange and electron-transfer dissociation mass spectrometry determine the interface and dynamics of apolipoprotein E oligomerization. Biochemistry, 2011, 50(43), 9273-9282.
Landgraf, R.R.; Chalmers, M.J.; Griffin, P.R. Automated hydrogen/deuterium exchange electron transfer dissociation high resolution mass spectrometry measured at single-amide resolution. J. Am. Soc. Mass Spectrom., 2012, 23(2), 301-309.
Pan, J.; Zhang, S.; Borchers, C.H. Comparative higher-order structure analysis of antibody biosimilars using combined bottom-up and top-down hydrogen-deuterium exchange mass spectrometry. Biochim. Biophys. Acta, 2016, 1864(12), 1801-1808.
Pan, J.; Han, J.; Borchers, C.H.; Konermann, L. Electron capture dissociation of electrosprayed protein ions for spatially resolved hydrogen exchange measurements. J. Am. Chem. Soc., 2008, 130(35), 11574-11575.
Abzalimov, R.R.; Kaplan, D.A.; Easterling, M.L.; Kaltashov, I.A. Protein conformations can be probed in top-down HDX MS experiments utilizing electron transfer dissociation of protein ions without hydrogen scrambling. J. Am. Soc. Mass Spectrom., 2009, 20(8), 1514-1517.
Pan, J.; Han, J.; Borchers, C.H.; Konermann, L. Conformer-specific hydrogen exchange analysis of Abeta(1-42) oligomers by top-down electron capture dissociation mass spectrometry. Anal. Chem., 2011, 83(13), 5386-5393.
Hamuro, Y. Regio-Selective intramolecular hydrogen/deuterium exchange in gas-phase electron transfer dissociation. J. Am. Soc. Mass Spectrom., 2017, 28(5), 971-977.
Hu, W.; Walters, B.T.; Kan, Z.Y.Y.; Mayne, L.; Rosen, L.E.; Marqusee, S.; Englander, S.W. Stepwise protein folding at near amino acid resolution by hydrogen exchange and mass spectrometry. Proc. Natl. Acad. Sci. USA, 2013, 110(19), 7684-7689.
Walters, B.T.; Mayne, L.; Hinshaw, J.R.; Sosnick, T.R.; Englander, S.W. Folding of a large protein at high structural resolution. Proc. Natl. Acad. Sci. USA, 2013, 110(47), 18898-18903.
Aghera, N.; Udgaonkar, J.B. Stepwise assembly of beta-sheet structure during the folding of an SH3 domain revealed by a pulsed hydrogen exchange mass spectrometry study. Biochemistry, 2017, 56(29), 3754-3769.
Pan, J.; Han, J.; Borchers, C.H.; Konermann, L. Characterizing short-lived protein folding intermediates by top-down hydrogen exchange mass spectrometry. Anal. Chem., 2010, 82(20), 8591-8597.
Zhang, Y.; Rempel, D.L.; Zhang, J.; Sharma, A.K.; Mirica, L.M.; Gross, M.L. Pulsed hydrogen-deuterium exchange mass spectrometry probes conformational changes in amyloid beta (Abeta) peptide aggregation. Proc. Natl. Acad. Sci. USA, 2013, 110(36), 14604-14609.
Anand, G.S.; Law, D.; Mandell, J.G.; Snead, A.N.; Tsigelny, I.; Taylor, S.S.; Ten Eyck, L.F.; Komives, E.A. Identification of the protein kinase A regulatory RIalpha-catalytic subunit interface by amide H/2H exchange and protein docking. Proc. Natl. Acad. Sci. USA, 2003, 100(23), 13264-13269.
Hsu, S.; Kim, Y.; Li, S.; Durrant, E.S.; Pace, R.M.; Woods, V.L. Jr.; Gentry, M.S. Structural insights into glucan phosphatase dynamics using amide hydrogen-deuterium exchange mass spectrometry. Biochemistry, 2009, 48(41), 9891-9902.
Harms, M.J.; Eick, G.N.; Goswami, D.; Colucci, J.K.; Griffin, P.R.; Ortlund, E.A.; Thornton, J.W. Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors. Proc. Natl. Acad. Sci. USA, 2013, 110(28), 11475-11480.
Noble, A.J.; Zhang, Q.; O’Donnell, J.; Hariri, H.; Bhattacharya, N.; Marshall, A.G.; Stagg, S.M. A pseudoatomic model of the COPII cage obtained from cryo-electron microscopy and mass spectrometry. Nat. Struct. Mol. Biol., 2013, 20(2), 167-173.
Zhang, Y.; Majumder, E.L.; Yue, H.; Blankenship, R.E.; Gross, M.L. Structural analysis of diheme cytochrome c by hydrogen-deuterium exchange mass spectrometry and homology modeling. Biochemistry, 2014, 53(35), 5619-5630.
Russel, D.; Lasker, K.; Webb, B.; Velazquez-Muriel, J.; Tjioe, E.; Schneidman-Duhovny, D.; Peterson, B.; Sali, A. Putting the pieces together: Integrative modeling platform software for structure determination of macromolecular assemblies. PLoS Biol., 2012, 10(1), e1001244.
Marcoux, J.; Cianferani, S. Towards integrative structural mass spectrometry: Benefits from hybrid approaches. Methods, 2015, 89, 4-12.
van Zundert, G.C.; Melquiond, A.S.; Bonvin, A.M. Integrative modeling of biomolecular complexes: HADDOCKing with cryo-electron microscopy data. Structure, 2015, 23(5), 949-960.
Huang, W.; Ravikumar, K.M.; Parisien, M.; Yang, S. Theoretical modeling of multiprotein complexes by iSPOT: Integration of small-angle X-ray scattering, hydroxyl radical footprinting, and computational docking. J. Struct. Biol., 2016, 196(3), 340-349.
Liu, T.; Pantazatos, D.; Li, S.; Hamuro, Y.; Hilser, V.J.; Woods, V.L.J. Quantitative assessment of protein structural models by comparison of H/D exchange MS data with exchange behavior accurately predicted by DXCOREX. J. Am. Soc. Mass Spectrom., 2012, 23(1), 43-56.
Saltzberg, D.J.; Broughton, H.B.; Pellarin, R.; Chalmers, M.J.; Espada, A.; Dodge, J.A.; Pascal, B.D.; Griffin, P.R.; Humblet, C.; Sali, A. A residue resolved bayesian approach to quantitative interpretation of hydrogen deuterium exchange from mass spectrometry: Application to characterizing protein-ligand interactions. J. Phys. Chem. B, 2017, 121(15), 3493-3501.
Truhlar, S.M.; Torpey, J.W.; Komives, E.A. Regions of IkappaBalpha that are critical for its inhibition of NF-kappaB.DNA interaction fold upon binding to NF-kappaB. Proc. Natl. Acad. Sci. USA, 2006, 103(50), 18951-18956.
Keppel, T.R.; Sarpong, K.; Murray, E.M.; Monsey, J.; Zhu, J.; Bose, R. Biophysical evidence for intrinsic disorder in the c-terminal tails of the EGFR and HER3 receptor tyrosine kinases. J. Biol. Chem., 2017, 292(2), 597-610.
Iacob, R.E.; Chen, G.; Ahn, J.; Houel, S.; Wei, H.; Mo, J.; Tao, L.; Cohen, D.; Xie, D.; Lin, Z.; Morin, P.E.; Doyle, M.L.; Tymiak, A.A.; Engen, J.R. The influence of adnectin binding on the extracellular domain of epidermal growth factor receptor. J. Am. Soc. Mass Spectrom., 2014, 25(12), 2093-2102.
Betts, G.N.; van der Geer, P.; Komives, E.A. Structural and functional consequences of tyrosine phosphorylation in the LRP1 cytoplasmic domain. J. Biol. Chem., 2008, 283(23), 15656-15664.
Devarakonda, S.; Gupta, K.; Chalmers, M.J.; Hunt, J.F.; Griffin, P.R.; Van Duyne, G.D.; Spiegelman, B.M. Disorder-to-order transition underlies the structural basis for the assembly of a transcriptionally active PGC-1α/ERRγ complex. Proc. Natl. Acad. Sci. USA, 2011, 108(46), 18678-18683.
Brown, K.A.; Sharifi, S.; Hussain, R.; Donaldson, L.; Bayfield, M.A.; Wilson, D.J. Distinct dynamic modes enable the engagement of dissimilar ligands in a promiscuous Atypical RNA recognition motif. Biochemistry, 2016, 55(51), 7141-7150.
Moulick, R.; Das, R.; Udgaonkar, J.B. Partially unfolded forms of the prion protein populated under misfolding-promoting conditions: Characterization by hydrogen exchange mass spectrometry and NMR. J. Biol. Chem., 2015, 290(42), 25227-25240.
Moulick, R.; Udgaonkar, J.B. Identification and structural characterization of the precursor conformation of the prion protein which directly initiates misfolding and oligomerization. J. Mol. Biol., 2017, 429(6), 886-899.
Singh, J.; Udgaonkar, J.B. Unraveling the molecular mechanism of pH-induced misfolding and oligomerization of the prion protein. J. Mol. Biol., 2016, 428(6), 1345-1355.
Balasubramaniam, D.; Komives, E.A. Hydrogen-exchange mass spectrometry for the study of intrinsic disorder in proteins. Biochim. Biophys. Acta, 2013, 1834(6), 1202-1209.
Wang, H.; Shu, Q.; Rempel, D.L.; Frieden, C.; Gross, M.L. Understanding curli amyloid-protein aggregation by hydrogen-deuterium exchange and mass spectrometry. Int. J. Mass Spectrom., 2017, 420, 16-23.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [16 - 26]
Pages: 11
DOI: 10.2174/0929866526666181212165037
Price: $65

Article Metrics

PDF: 36