title: Probing serpin conformational change using mass spectrometry and related methods.
abstract: The folding, misfolding, and inhibitory mechanisms of serpins are linked to both thermodynamic metastability and conformational flexibility. Characterizing the structural distribution of stability and flexibility in serpins in solution is challenging due to their large size and propensity for aggregation. Structural mass spectrometry techniques offer powerful tools for probing the mechanisms of serpin function and disfunction. In this chapter, we review the principles of the two most commonly employed structural mass spectrometry techniques--hydrogen/deuterium exchange and chemical footprinting--and describe their application to studying serpin flexibility, stability, and conformational change in solution. We also review the application of both hydrogen/deuterium exchange and ion mobility mass spectrometry to probe the mechanism of serpin polymerization and the structure of serpin polymers.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USA.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsutsui
authors.forename: Anindya
authors.initials: A
authors.lastname: Sarkar
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Wintrode
mesh_terms: D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D041961:Deuterium Exchange Measurement / Q000379:methods*; D006031:Glycosylation; D006801:Humans; D006859:Hydrogen / Q000737:chemistry* / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods*; D007700:Kinetics; D013058:Mass Spectrometry / Q000379:methods*; D008958:Models, Molecular; D009154:Mutation; D058105:Polymerization; D011487:Protein Conformation; D058767:Protein Unfolding; D011994:Recombinant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics; D000515:alpha 1-Antitrypsin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D000515:alpha 1-Antitrypsin; D006859:Hydrogen
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