2. Academic Validation
  3. The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation

The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation

  • Nat Commun. 2025 Mar 11;16(1):2436. doi: 10.1038/s41467-025-57768-9.
Junjiang Peng # 1 2,  Wenguo Li # 1 2,  Deqiang Yao # 3,  Ying Xia 2,  Qian Wang 2,  Yan Cai 2,  Shaobai Li 2,  Mi Cao 2,  Yafeng Shen 2,  Peixiang Ma 1 4,  Rijing Liao 2,  Jie Zhao 1 4,  An Qin 5 6,  Yu Cao 7 8
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
  • 2 Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, Shanghai, 200125, China.
  • 3 Institute of Aging & Tissue Regeneration, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, 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, 200011, China.
  • 5 Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. dr_qinan@163.com.
  • 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, 200011, China. dr_qinan@163.com.
  • 7 Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. yu.cao@shsmu.edu.cn.
  • 8 Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, Shanghai, 200125, China. yu.cao@shsmu.edu.cn.
  • # Contributed equally.
PMID: 40069201 DOI: 10.1038/s41467-025-57768-9
Abstract

The proper assembly and maturation of collagens necessitate the orchestrated hydroxylation and glycosylation of multiple lysyl residues in procollagen chains. Dysfunctions in this multistep modification process can lead to severe collagen-associated diseases. To elucidate the coordination of lysyl processing activities, we determine the cryo-EM structures of the enzyme complex formed by LH3/PLOD3 and GLT25D1/ColGalT1, designated as the KOGG complex. Our structural analysis reveals a tetrameric complex comprising dimeric LH3/PLOD3s and GLT25D1/ColGalT1s, assembled with interactions involving the N-terminal loop of GLT25D1/ColGalT1 bridging another GLT25D1/ColGalT1 and LH3/PLOD3. We further elucidate the spatial configuration of the hydroxylase, galactosyltransferase, and glucosyltransferase sites within the KOGG complex, along with the key residues involved in substrate binding at these enzymatic sites. Intriguingly, we identify a high-order oligomeric pattern characterized by the formation of a fiber-like KOGG polymer assembled through the repetitive incorporation of KOGG tetramers as the biological unit.

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