Functional unfolding of alpha1-antitrypsin probed by hydrogen-deuterium exchange coupled with mass spectrometry.

ABSTRACT: The native state of alpha(1)-antitrypsin (alpha(1)AT), a member of the serine protease inhibitor (serpin) family, is considered a kinetically trapped folding intermediate that converts to a more stable form upon complex formation with a target protease. Although previous structural and mutational studies of alpha(1)AT revealed the structural basis of the native strain and the kinetic trap, the mechanism of how the native molecule overcomes the kinetic barrier to reach the final stable conformation during complex formation remains unknown. We hypothesized that during complex formation, a substantial portion of the molecule undergoes unfolding, which we dubbed functional unfolding. Hydrogen-deuterium exchange coupled with ESI-MS was used to analyze this serpin in three forms: native, complex

SUBMITTER: Baek JH 

PROVIDER: S-EPMC2689767 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature