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

被引：44

作者：

Krishnan, Beena ^{[1
]}

Gierasch, Lila M. ^{[1
,2
]}

机构：

[1] Univ Massachusetts, Dept Biochem & Mol Biol, Amherst, MA 01003 USA

[2] Univ Massachusetts, Dept Chem, Amherst, MA 01003 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2011年 / 18卷 / 02期

基金：

美国国家卫生研究院;

关键词：

PLASMINOGEN-ACTIVATOR INHIBITOR-1; ALPHA(1)-ANTITRYPSIN DEFICIENCY; FOLDING DEFECT; HYDROGEN-BOND; IN-VIVO; STABILITY; REVEALS; DISEASE; SITE;

D O I：

10.1038/nsmb.1976

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 alpha-1 antitrypsin (alpha(1)AT) and show how local unfolding allows functionally essential strand insertion. Mutations in alpha(1)AT 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.

引用

页码：222 / U288

页数：6

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