Poly(ADP-ribose) binding sites on collagen I fibrils for nucleating intrafibrillar bone mineral
Bone calcification is essential for vertebrate life. The mechanism by which mineral ions are transported into collagen fibrils to induce intrafibrillar mineral formation requires a calcium binding biopolymer that also has highly selective binding to the collagen fibril hole zones where intrafibrillar calcification begins, over other bone extracellular matrix components. Poly(ADP-ribose) (PAR) has been shown to be a candidate biopolymer for this process and we show here that PAR has high affinity, highly conserved binding sites in the collagen type I C-terminal telopeptides. The identification of these PAR-collagen binding sites gives insights into the chemical mechanisms underlying bone calcification and possible mechanisms behind pathologies where there is dysfunctional bone calcification.
Authors
- Melinda J. Duer (ORCID: https://orcid.org/0000-0002-9196-5072)
- Karin H. Müller (ORCID: https://orcid.org/0000-0003-4693-8558)
- Heather F. Greer (ORCID: https://orcid.org/0000-0001-6149-1964)
- Marco A. Zecca (ORCID: https://orcid.org/0000-0002-6184-8940)
Institutions
- University of Cambridge (GB)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-02-20
- DOI
- https://doi.org/10.1073/pnas.2414849122
- Citations
- 7
- Primary Topic
- Bone and Dental Protein Studies
- Type
- article
- Field-Weighted Citation Impact
- 11.68
Funders
- European Commission
- Engineering and Physical Sciences Research Council
- HORIZON EUROPE European Research Council