University of Oulu

Abhinandan V. Murthy, Ramita Sulu, Andrey Lebedev, Antti M. Salo, Kati Korhonen, Rajaram Venkatesan, Hongmin Tu, Ulrich Bergmann, Janne Jänis, Mikko Laitaoja, Lloyd W. Ruddock, Johanna Myllyharju, M. Kristian Koski, Rik K. Wierenga, Crystal structure of the collagen prolyl 4-hydroxylase (C-P4H) catalytic domain complexed with PDI: Toward model of the C-P4H α2β2 tetramer, Journal of Biological Chemistry, Volume 298, Issue 12, 2022, 102614, ISSN 0021-9258,

Crystal structure of the collagen prolyl 4-hydroxylase (C-P4H) catalytic domain complexed with PDI : toward a model of the C-P4H α₂β₂ tetramer

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Author: Murthy, Abhinandan V.1,2; Sulu, Ramita1; Lebedev, Andrey3;
Organizations: 1Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
2Biocenter Oulu, University of Oulu, Oulu, Finland
3Scientific Computing Department, STFC Rutherford Appleton Lab., RCaH, Harwell Campus, Didcot, United Kingdom
4Department of Chemistry, University of Eastern Finland, Joensuu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.8 MB)
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Language: English
Published: American Society for Biochemistry and Molecular Biology, 2022
Publish Date: 2022-12-20


Collagen prolyl 4-hydroxylases (C-P4H) are α₂β₂ tetramers, which catalyze the prolyl 4-hydroxylation of procollagen, allowing for the formation of the stable triple-helical collagen structure in the endoplasmic reticulum. The C-P4H α-subunit provides the N-terminal dimerization domain, the middle peptide-substrate-binding (PSB) domain, and the C-terminal catalytic (CAT) domain, whereas the β-subunit is identical to the enzyme protein disulfide isomerase (PDI). The structure of the N-terminal part of the α-subunit (N-terminal region and PSB domain) is known, but the structures of the PSB-CAT linker region and the CAT domain as well as its mode of assembly with the β/PDI subunit, are unknown. Here, we report the crystal structure of the CAT domain of human C-P4H-II complexed with the intact β/PDI subunit, at 3.8 Å resolution. The CAT domain interacts with the a, b’, and a’ domains of the β/PDI subunit, such that the CAT active site is facing bulk solvent. The structure also shows that the C-P4H-II CAT domain has a unique N-terminal extension, consisting of α-helices and a β-strand, which is the edge strand of its major antiparallel β-sheet. This extra region of the CAT domain interacts tightly with the β/PDI subunit, showing that the CAT-PDI interface includes an intersubunit disulfide bridge with the a’ domain and tight hydrophobic interactions with the b’ domain. Using this new information, the structure of the mature C-P4H-II α₂β₂ tetramer is predicted. The model suggests that the CAT active-site properties are modulated by α-helices of the N-terminal dimerization domains of both subunits of the α₂-dimer.

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Series: Journal of biological chemistry
ISSN: 0021-9258
ISSN-E: 1083-351X
ISSN-L: 0021-9258
Volume: 298
Issue: 12
Pages: 1 - 17
Article number: 102614
DOI: 10.1016/j.jbc.2022.102614
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This study was supported by the Academy of Finland through Academy Project grant 296498 (to J. M.) and Center of Excellence 2012 to 2017 grant 251314 (to J. M.), by the S. Jusélius Foundation (to J. M.) and the Jane and Aatos Erkko Foundation (to J. M.) as well as by the Academy of Finland grant 318182 (to L. W. R.) and by a grant from the Sigrid Jusélius Foundation (to M. K. K./R. K. W.).
Academy of Finland Grant Number: 251314
Detailed Information: 251314 (Academy of Finland Funding decision)
296498 (Academy of Finland Funding decision)
318182 (Academy of Finland Funding decision)
Copyright information: © 2022 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (