title: Investigation of protein folding by mass spectrometry.
abstract: 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.
authors.affiliation: Oxford Centre for Molecular Sciences and New Chemistry Laboratory, University of Oxford, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Miranker
authors.forename: C V
authors.initials: CV
authors.lastname: Robinson
authors.forename: S E
authors.initials: SE
authors.lastname: Radford
authors.forename: C M
authors.initials: CM
authors.lastname: Dobson
mesh_terms: D018834:Chaperonin 60 / Q000737:chemistry; D018833:Chaperonins / Q000378:metabolism; D007700:Kinetics; D007768:Lactalbumin / Q000737:chemistry*; D008024:Ligands; D013058:Mass Spectrometry / Q000379:methods*; D009113:Muramidase / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D018834:Chaperonin 60; D008024:Ligands; D007768:Lactalbumin; D009113:Muramidase; D018833:Chaperonins