Complementary Structural Mass Spectrometry Techniques Reveal Local Dynamics in Functionally Important Regions of a Metastable Serpin

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Structure

DOI:https://doi.org/10.1016/j.str.2007.10.019· OSTI ID:959983

Zheng, X; Wintrode, P; Chance, M

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, a1-antitrypsin (a1AT). H/D exchange revealed the distribution of flexible and rigid regions of a1AT, whereas footprinting revealed the dynamic environments of several side chains previously identified as important for the metastability of a1AT. This work provides insights into the unique structural design of a1AT 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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 959983
• Report Number(s): BNL--82969-2009-JA
• Journal Information: Structure, Journal Name: Structure Journal Issue: 1 Vol. 16
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CHAINS
CRYSTAL STRUCTURE
CRYSTALLOGRAPHY
DESIGN
DISTRIBUTION
MASS SPECTROSCOPY
PROTEIN STRUCTURE
national synchrotron light source