title: Complementary structural mass spectrometry techniques reveal local dynamics in functionally important regions of a metastable serpin.
abstract: Serpins display a number of highly unusual structural properties along with a unique mechanism of inhibition. Although structures of numerous serpins have been solved by X-ray crystallography, little is known about the dynamics of serpins in their inhibitory active conformation. In this study, two complementary structural mass spectrometry methods, hydroxyl radical-mediated footprinting and hydrogen/deuterium (H/D) exchange, were employed to highlight differences between the static crystal structure and the dynamic conformation of human serpin protein, alpha(1)-antitrypsin (alpha(1)AT). H/D exchange revealed the distribution of flexible and rigid regions of alpha(1)AT, whereas footprinting revealed the dynamic environments of several side chains previously identified as important for the metastability of alpha(1)AT. This work provides insights into the unique structural design of alpha(1)AT and improves our understanding of its unusual inhibition mechanism. Also, we demonstrate that the combination of the two MS techniques provides a more complete picture of protein structure than either technique alone.
authors.affiliation: Case Center for Proteomics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zheng
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Wintrode
authors.forename: Mark R
authors.initials: MR
authors.lastname: Chance
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003903:Deuterium; D004355:Drug Stability; D006859:Hydrogen; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010449:Peptide Mapping; D011487:Protein Conformation; D015843:Serpins / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D010446:Peptide Fragments; D015843:Serpins; D006859:Hydrogen; D003903:Deuterium