1QMB

Cleaved alpha-1-antitrypsin polymer

1QMB の概要

• エントリーDOI: 10.2210/pdb1qmb/pdb
• 関連するPDBエントリー: 1ATU 1KCT 1PSI 2PSI 7API 8API 9API
• 分子名称: ALPHA-1-ANTITRYPSIN (3 entities in total)
• 機能のキーワード: serine protease inhibitor, serpin, antitrypsin, polymer, cleaved
• 由来する生物種: HOMO SAPIENS; 詳細
• 細胞内の位置: Secreted. Short peptide from AAT: Secreted, extracellular space, extracellular matrix: P01009 P01009
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41386.39

構造登録者

Huntington, J.A.,Pannu, N.S.,Hazes, B.,Read, R.J.,Lomas, D.A.,Carrell, R.W. (登録日: 1999-09-24, 公開日: 2000-02-06, 最終更新日: 2023-12-13)

主引用文献

Huntington, J.A.,Pannu, N.S.,Hazes, B.,Read, R.J.,Lomas, D.A.,Carrell, R.W.
A 2.6A Structure of a Serpin Polymer and Implications for Conformational Disease
J.Mol.Biol., 293:449-, 1999

PubMed Abstract: The function of the serpins as proteinase inhibitors depends on their ability to insert the cleaved reactive centre loop as the fourth strand in the main A beta-sheet of the molecule upon proteolytic attack at the reactive centre, P1-P1'. This mechanism is vulnerable to mutations which result in inappropriate intra- or intermolecular loop insertion in the absence of cleavage. Intermolecular loop insertion is known as serpin polymerisation and results in a variety of diseases, most notably liver cirrhosis resulting from mutations of the prototypical serpin alpha1-antitrypsin. We present here the 2.6 A structure of a polymer of alpha1-antitrypsin cleaved six residues N-terminal to the reactive centre, P7-P6 (Phe352-Leu353). After self insertion of P14 to P7, intermolecular linkage is affected by insertion of the P6-P3 residues of one molecule into the partially occupied beta-sheet A of another. This results in an infinite, linear polymer which propagates in the crystal along a 2-fold screw axis. These findings provide a framework for understanding the uncleaved alpha1-antitrypsin polymer and fibrillar and amyloid deposition of proteins seen in other conformational diseases, with the ordered array of polymers in the crystal resulting from slow accretion of the cleaved serpin over the period of a year.

PubMed: 10543942
DOI: 10.1006/JMBI.1999.3184

実験手法

X-RAY DIFFRACTION (2.6 Å)