The FASEB Journal, Vol 10, 93-101, Copyright © 1996 by The Federation of American Societies for Experimental Biology

REVIEWS

Investigation of protein folding by mass spectrometry

A Miranker, CV Robinson, SE Radford and CM Dobson
Oxford Centre for Molecular Sciences and New Chemistry Laboratory, University of Oxford, United Kingdom.

Mass spectrometry is emerging as one of the most exciting new techniques being applied to studies of protein folding. Recent developments in soft ionization techniques enable intact proteins to be generated in the gas phase from aqueous solution, and fragmentation methods are providing a means of obtaining sequence-specific information. These techniques, particularly in combination with established methods such as NMR spectroscopy, allow the investigation of both covalent and noncovalent events that occur during refolding processes. One important type of application involves mass spectrometry in an analytical role, for example, in characterizing the products of oxidative refolding experiments. Mass spectrometry can also be used to reveal fundamentally new information about the conformational properties of folding intermediates, both in isolation and in complexes with molecular chaperones, through the exploitation of hydrogen- deuterium exchange phenomena. Of particular interest is the insight this approach can provide into the cooperativity of structure formation and the distribution of intermediates at different steps along folding pathways. In this paper we describe recent insights into protein folding resulting from the application of mass spectrometry and discuss the future potential of the method for studies in this area.

This article has been cited by other articles:

				S. S. Jaswal and A. D. Miranker Scope and utility of hydrogen exchange as a tool for mapping landscapes Protein Sci., November 1, 2007; 16(11): 2378 - 2390. [Abstract] [Full Text] [PDF]

				H. D. White and A. E. Ashcroft Real-Time Measurement of Myosin-Nucleotide Noncovalent Complexes by Electrospray Ionization Mass Spectrometry Biophys. J., August 1, 2007; 93(3): 914 - 919. [Abstract] [Full Text] [PDF]

				M. Xu, V. A. Shashilov, V. V. Ermolenkov, L. Fredriksen, D. Zagorevski, and I. K. Lednev The first step of hen egg white lysozyme fibrillation, irreversible partial unfolding, is a two-state transition Protein Sci., May 1, 2007; 16(5): 815 - 832. [Abstract] [Full Text] [PDF]

				B. F. Shaw, A. Durazo, A. M. Nersissian, J. P. Whitelegge, K. F. Faull, and J. S. Valentine Local Unfolding in a Destabilized, Pathogenic Variant of Superoxide Dismutase 1 Observed with H/D Exchange and Mass Spectrometry J. Biol. Chem., June 30, 2006; 281(26): 18167 - 18176. [Abstract] [Full Text] [PDF]

				J. A. Rodriguez, B. F. Shaw, A. Durazo, S. H. Sohn, P. A. Doucette, A. M. Nersissian, K. F. Faull, D. K. Eggers, A. Tiwari, L. J. Hayward, et al. Destabilization of apoprotein is insufficient to explain Cu,Zn-superoxide dismutase-linked ALS pathogenesis PNAS, July 26, 2005; 102(30): 10516 - 10521. [Abstract] [Full Text] [PDF]

				D. Varrazzo, A. Bernini, O. Spiga, A. Ciutti, S. Chiellini, V. Venditti, L. Bracci, and N. Niccolai Three-dimensional computation of atom depth in complex molecular structures Bioinformatics, June 15, 2005; 21(12): 2856 - 2860. [Abstract] [Full Text] [PDF]

				X. Yan, J. Watson, P. S. Ho, and M. L. Deinzer Mass Spectrometric Approaches Using Electrospray Ionization Charge States and Hydrogen-Deuterium Exchange for Determining Protein Structures and Their Conformational Changes Mol. Cell. Proteomics, January 1, 2004; 3(1): 10 - 23. [Abstract] [Full Text] [PDF]

				R. K. Chitta and M. L. Gross Electrospray Ionization-Mass Spectrometry and Tandem Mass Spectrometry Reveal Self-Association and Metal-Ion Binding of Hydrophobic Peptides: A Study of the Gramicidin Dimer Biophys. J., January 1, 2004; 86(1): 473 - 479. [Abstract] [Full Text] [PDF]

				R. Grandori Detecting equilibrium cytochrome c folding intermediates by electrospray ionisation mass spectrometry: Two partially folded forms populate the molten-globule state Protein Sci., March 1, 2002; 11(3): 453 - 458. [Abstract] [Full Text] [PDF]

				A. D. Miranker Mass spectrometry of proteins of known mass PNAS, December 8, 2000; (2000) 11526498. [Full Text]

				I. Kheterpal, S. Zhou, K. D. Cook, and R. Wetzel Abeta amyloid fibrils possess a core structure highly resistant to hydrogen exchange PNAS, November 16, 2000; (2000) 250288897. [Abstract] [Full Text]

				S. Ghaemmaghami, M. C. Fitzgerald, and T. G. Oas A quantitative, high-throughput screen for protein stability PNAS, July 5, 2000; (2000) 140111397. [Abstract] [Full Text]

				B. Bothner, R. Chavez, J. Wei, C. Strupp, Q. Phung, A. Schneemann, and G. Siuzdak Monitoring Enzyme Catalysis with Mass Spectrometry J. Biol. Chem., April 28, 2000; 275(18): 13455 - 13459. [Abstract] [Full Text] [PDF]

				M. J. Pandya, P. B. Williams, C. E. Dempsey, P. R. Shewry, and A. R. Clarke Direct Kinetic Evidence for Folding via a Highly Compact, Misfolded State J. Biol. Chem., September 17, 1999; 274(38): 26828 - 26837. [Abstract] [Full Text] [PDF]

				D. R. Benjamin, C. V. Robinson, J. P. Hendrick, F. U. Hartl, and C. M. Dobson Mass spectrometry of ribosomes and ribosomal subunits PNAS, June 23, 1998; 95(13): 7391 - 7395. [Abstract] [Full Text] [PDF]

				A. D. Miranker Mass spectrometry of proteins of known mass PNAS, December 19, 2000; 97(26): 14025 - 14027. [Full Text] [PDF]

				S. Ghaemmaghami, M. C. Fitzgerald, and T. G. Oas A quantitative, high-throughput screen for protein stability PNAS, July 18, 2000; 97(15): 8296 - 8301. [Abstract] [Full Text] [PDF]

				I. Kheterpal, S. Zhou, K. D. Cook, and R. Wetzel Abeta amyloid fibrils possess a core structure highly resistant to hydrogen exchange PNAS, December 5, 2000; 97(25): 13597 - 13601. [Abstract] [Full Text] [PDF]