The structural basis for the collagen processing by human P3H1/CRTAP/PPIB ternary complex

  • Nat Commun. 2024 Sep 8;15(1):7844. doi: 10.1038/s41467-024-52321-6.
Wenguo Li  #  1  2 ,  Junjiang Peng  #  2 ,  Deqiang Yao  #  3 ,  Bing Rao  1  4 ,  Ying Xia  2 ,  Qian Wang  2 ,  Shaobai Li  2 ,  Mi Cao  2 ,  Yafeng Shen  2 ,  Peixiang Ma  1  4 ,  Rijing Liao  2 ,  An Qin  5  6 ,  Jie Zhao  7  8 ,  Yu Cao  9  10
Affiliations
  • 1. Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2. Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, Shanghai, China.
  • 3. Institute of Aging & Tissue Regeneration, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4. Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5. Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 6. Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 7. Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 8. Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 9. Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 10. Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 39245686 DOI: 10.1038/s41467-024-52321-6
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.