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

Nat Commun

Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Published: September 2024

AI Article Synopsis

  • - Collagen processing is essential for its proper function, and disruptions can cause disorders like osteogenesis imperfecta (OI), which affects tissue development and structure.
  • - Researchers studied the structure of a complex involving prolyl 3-hydroxylase 1 (P3H1), peptidyl-prolyl cis-trans isomerase B (PPIB), and cartilage-associated protein (CRTAP) using cryo-electron microscopy, revealing a unique mechanism involving multiple binding sites.
  • - The study found that mutations and inhibitors can shift the balance between different complex states, offering new insights into the mechanisms behind collagen processing and associated diseases.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381544PMC
http://dx.doi.org/10.1038/s41467-024-52321-6DOI Listing

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