2K18

Solution structure of bb' domains of human protein disulfide isomerase

2K18 の概要

• エントリーDOI: 10.2210/pdb2k18/pdb
• 関連するPDBエントリー: 1BJX
• 分子名称: Protein disulfide-isomerase (1 entity in total)
• 機能のキーワード: pdi, endoplasmic reticulum, disulfide bonds, protein folding, chaperone, isomerase, membrane, redox-active center
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum lumen: P07237
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25564.93

構造登録者

Denisov, A.Y.,Maattanen, P.,Dabrowski, C.,Kozlov, G.,Thomas, D.Y.,Gehring, K. (登録日: 2008-02-22, 公開日: 2008-04-29, 最終更新日: 2024-05-29)

主引用文献

Denisov, A.Y.,Maattanen, P.,Dabrowski, C.,Kozlov, G.,Thomas, D.Y.,Gehring, K.
Solution structure of the bb' domains of human protein disulfide isomerase.
Febs J., 276:1440-1449, 2009

PubMed Abstract: Protein disulfide isomerase is the most abundant and best studied of the disulfide isomerases that catalyze disulfide bond formation in the endoplasmic reticulum, yet the specifics of how it binds substrate have been elusive. Protein disulfide isomerase is composed of four thioredoxin-like domains (abb'a'). Cross-linking studies with radiolabeled peptides and unfolded proteins have shown that it binds incompletely folded proteins primarily via its third domain, b'. Here, we determined the solution structure of the second and third domains of human protein disulfide isomerase (b and b', respectively) by triple-resonance NMR spectroscopy and molecular modeling. NMR titrations identified a large hydrophobic surface within the b' domain that binds unfolded ribonuclease A and the peptides mastoparan and somatostatin. Protein disulfide isomerase-catalyzed refolding of reduced ribonuclease A in vitro was inhibited by these peptides at concentrations equal to their affinity to the bb' fragment. Our findings provide a structural basis for previous kinetic and cross-linking studies which have shown that protein disulfide isomerase exhibits a saturable, substrate-binding site.

PubMed: 19187238
DOI: 10.1111/j.1742-4658.2009.06884.x

実験手法

SOLUTION NMR