期刊
EMBO REPORTS
卷 12, 期 10, 页码 1011-1017出版社
WILEY
DOI: 10.1038/embor.2011.171
关键词
serpin; crystal structure; polymer; domain swap
资金
- Diamond Light Source
- MRC [G0801899] Funding Source: UKRI
- Medical Research Council [G0801899] Funding Source: researchfish
alpha(1)-Antitrypsin (alpha 1AT) deficiency is a disease with multiple manifestations, including cirrhosis and emphysema, caused by the accumulation of stable polymers of mutant protein in the endoplasmic reticulum of hepatocytes. However, the molecular basis of misfolding and polymerization remain unknown. We produced and crystallized a trimeric form of alpha 1AT that is recognized by an antibody specific for the pathological polymer. Unexpectedly, this structure reveals a polymeric linkage mediated by domain swapping the carboxy-terminal 34 residues. Disulphide-trapping and antibody-binding studies further demonstrate that runaway C-terminal domain swapping, rather than the s4A/s5A domain swap previously proposed, underlies polymerization of the common Z-mutant of alpha 1AT in vivo.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据