3T1P

Crystal structure of an alpha-1-antitrypsin trimer

3T1P の概要

• エントリーDOI: 10.2210/pdb3t1p/pdb
• 分子名称: Alpha-1-antitrypsin (1 entity in total)
• 機能のキーワード: serpin, protease inhibitor, plasma, hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted. Short peptide from AAT: Secreted, extracellular space, extracellular matrix: P01009
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41842.86

構造登録者

Huntington, J.A.,Yamasaki, M. (登録日: 2011-07-22, 公開日: 2011-08-17, 最終更新日: 2024-11-06)

主引用文献

Yamasaki, M.,Sendall, T.J.,Pearce, M.C.,Whisstock, J.C.,Huntington, J.A.
Molecular basis of alpha 1-antitrypsin deficiency revealed by the structure of a domain-swapped trimer.
EMBO Rep., 12:1011-1017, 2011

PubMed Abstract: α(1)-Antitrypsin (α1AT) 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 α1AT 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 α1AT in vivo.

PubMed: 21909074
DOI: 10.1038/embor.2011.171

実験手法

X-RAY DIFFRACTION (3.9 Å)