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Tissue-specific collagen hydroxylation at GEP/GDP triplets mediated by P4HA2.
- Source :
-
Matrix Biology . May2023, Vol. 119, p141-153. 13p. - Publication Year :
- 2023
-
Abstract
- 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 a 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0945053X
- Volume :
- 119
- Database :
- Academic Search Index
- Journal :
- Matrix Biology
- Publication Type :
- Academic Journal
- Accession number :
- 163424404
- Full Text :
- https://doi.org/10.1016/j.matbio.2023.03.009