Altered native stability is the dominant basis for susceptibility of α1-antitrypsin mutants to polymerization.

ABSTRACT: Serpins are protease inhibitors whose most stable state is achieved upon transition of a central 5-stranded β-sheet to a 6-stranded form. Mutations, low pH, denaturants and elevated temperatures promote this transition, which can result in a growing polymer chain of inactive molecules. Different types of polymer are possible, but, experimentally only heat has been shown to generate polymers in vitro consistent with ex vivo pathological specimens. Many mutations that alter the rate of heat-induced polymerization have been described, but interpretation is problematic because discrimination is lacking between the effect of global changes in native stability and specific effects on structural mechanism. We show that the temperature midpoint (Tm) of thermal denaturation reflects the transition

SUBMITTER: Irving JA 

PROVIDER: S-EPMC4080824 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature