Dynamic local unfolding in the serpin α-1 antitrypsin provides a mechanism for loop insertion and polymerization.

ABSTRACT: The conformational plasticity of serine protease inhibitors (serpins) underlies both their activities as protease inhibitors and their susceptibility to pathogenic misfolding and aggregation. Here, we structurally characterize a sheet-opened state of the serpin α-1 antitrypsin (α₁AT) and show how local unfolding allows functionally essential strand insertion. Mutations in α₁AT that cause polymerization-induced serpinopathies map to the labile region, suggesting that the evolution of serpin function required sampling of high risk conformations on a dynamic energy landscape.

SUBMITTER: Krishnan B 

PROVIDER: S-EPMC3074950 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature