8K0E

Human collagen prolyl processing enzyme complex, P3H1/CRTAP heterodimer

8K0E の概要

• エントリーDOI: 10.2210/pdb8k0e/pdb
• EMDBエントリー: 36762
• 分子名称: Prolyl 3-hydroxylase 1, Cartilage-associated protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: complex, hydroxylase, collagen, er protein, cytosolic protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 135988.36

構造登録者

Li, W.,Peng, J.,Yao, D.,Rao, B.,Xia, Y.,Wang, Q.,Li, S.,Cao, M.,Shen, Y.,Ma, P.,Liao, R.,Qin, A.,Zhao, J.,Cao, Y. (登録日: 2023-07-08, 公開日: 2024-09-18, 最終更新日: 2024-11-13)

主引用文献

Li, W.,Peng, J.,Yao, D.,Rao, B.,Xia, Y.,Wang, Q.,Li, S.,Cao, M.,Shen, Y.,Ma, P.,Liao, R.,Qin, A.,Zhao, J.,Cao, Y.
The structural basis for the collagen processing by human P3H1/CRTAP/PPIB ternary complex.
Nat Commun, 15:7844-7844, 2024

PubMed Abstract: Collagen posttranslational processing is crucial for its proper assembly and function. Disruption of collagen processing leads to tissue development and structure disorders like osteogenesis imperfecta (OI). OI-related collagen processing machinery includes prolyl 3-hydroxylase 1 (P3H1), peptidyl-prolyl cis-trans isomerase B (PPIB), and cartilage-associated protein (CRTAP), with their structural organization and mechanism unclear. We determine cryo-EM structures of the P3H1/CRTAP/PPIB complex. The active sites of P3H1 and PPIB form a face-to-face bifunctional reaction center, indicating a coupled modification mechanism. The structure of the P3H1/CRTAP/PPIB/collagen peptide complex reveals multiple binding sites, suggesting a substrate interacting zone. Unexpectedly, a dual-ternary complex is observed, and the balance between ternary and dual-ternary states can be altered by mutations in the P3H1/PPIB active site and the addition of PPIB inhibitors. These findings provide insights into the structural basis of collagen processing by P3H1/CRTAP/PPIB and the molecular pathology of collagen-related disorders.

PubMed: 39245686
DOI: 10.1038/s41467-024-52321-6

実験手法

ELECTRON MICROSCOPY (3.65 Å)