Tissue-specific collagen hydroxylation at GEP/GDP triplets mediated by P4HA2.
Fiche publication
Date publication
mars 2023
Journal
Matrix biology : journal of the International Society for Matrix Biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VINCOURT Jean-Baptiste
Tous les auteurs :
Wilhelm D, Wurtz A, Abouelfarah H, Sanchez G, Bui C, Vincourt JB
Lien Pubmed
Résumé
Collagen, the most abundant organic compound of vertebrate organisms, is a supramolecular, protein-made polymer. Details of its post-translational maturation largely determine the mechanical properties of connective tissues. Its assembly requires massive, heterogeneous prolyl-4-hydroxylation (P4H), catalyzed by Prolyl-4-hydroxylases (P4HA1-3), providing thermostability to its elemental, triple helical building block. So far, there was no evidence of tissue-specific regulation of P4H, nor of a differential substrate repertoire of P4HAs. Here, the post-translational modifications of collagen extracted from bone, skin, and tendon were compared, revealing lower hydroxylation of most GEP/GDP triplets, together with fewer other residue positions along collagen α chains, in the tendon. This regulation is mostly conserved in two distant homeotherm species, mouse and chicken. The comparison of detailed P4H patterns in both species suggests a two-step mechanism of specificity. P4ha2 expression is low in tendon and its genetic invalidation in the ATDC5 cellular model of collagen assembly specifically mimics the tendon-related P4H profile. Therefore, P4HA2 has a better ability than other P4HAs to hydroxylate the corresponding residue positions. Its local expression participates in determining the P4H profile, a novel aspect of the tissue specificities of collagen assembly. Data availability: Proteomics data are available via ProteomeXchange with the identifier PXD039221. Reviewer account details.
Mots clés
4-hydroxyproline, bone, mass spectrometry, prolyl-4-hydroxylase, relative quantification, skin, tendon, type I collagen
Référence
Matrix Biol. 2023 03 30;: