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- Title
The structural basis for the collagen processing by human P3H1/CRTAP/PPIB ternary complex.
- Authors
Li, Wenguo; Peng, Junjiang; Yao, Deqiang; Rao, Bing; Xia, Ying; Wang, Qian; Li, Shaobai; Cao, Mi; Shen, Yafeng; Ma, Peixiang; Liao, Rijing; Qin, An; Zhao, Jie; Cao, Yu
- 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. Collagen requires complicated modifications for proper assembly. Here, the authors show the structural basis of human collagen processing by the P3H1/CRTAP/PPIB complex, revealing a 'face-to-face' catalytic site configuration, collagen binding sites, and transition between trimer and hexamer states.
- Subjects
OSTEOGENESIS imperfecta; PEPTIDES; MOLECULAR pathology; EIGENFUNCTIONS; BINDING sites
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-52321-6