The structural basis of serpin polymerization studied by hydrogen/deuterium exchange and mass spectrometry.

ABSTRACT: The serpinopathies are a group of inherited disorders that share as their molecular basis the misfolding and polymerization of serpins, an important class of protease inhibitors. Depending on the identity of the serpin, conditions arising from polymerization include emphysema, thrombosis, and dementia. The structure of serpin polymers is thus of considerable medical interest. Wild-type alpha(1)-antitrypsin will form polymers upon incubation at moderate temperatures and has been widely used as a model system for studying serpin polymerization. Using hydrogen/deuterium exchange and mass spectrometry, we have obtained molecular level structural information on the alpha(1)-antitrypsin polymer. We found that the flexible reactive center loop becomes strongly protected upon polymerization. We al

SUBMITTER: Tsutsui Y 

PROVIDER: S-EPMC2576545 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature