Collagen VI microfibril structure reveals mechanism for molecular assembly and clustering of inherited pathogenic mutations

Alan R. F. Godwin, Mark H. Becker, Rana Dajani, Matthew Snee, Alan M. Roseman and Clair Baldock ()
Additional contact information
Alan R. F. Godwin: University of Manchester
Mark H. Becker: University of Manchester
Rana Dajani: University of Manchester
Matthew Snee: University of Manchester
Alan M. Roseman: University of Manchester
Clair Baldock: University of Manchester

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Collagen VI links the cell surface to the extracellular matrix to provide mechanical strength to most mammalian tissues, and is linked to human diseases including muscular dystrophy, fibrosis, cardiovascular disease and osteoarthritis. Collagen VI assembles from heterotrimers of three different α-chains into microfibrils, but there are many gaps in our knowledge of the molecular assembly process. Here, we determine the structures of both heterotrimeric mini-collagen VI constructs and collagen VI microfibrils, from mammalian tissue, using cryogenic-electron microscopy. These structures reveal a cysteine-rich coiled coil region involved in trimerisation as well as microfibril assembly. Furthermore, our structures show that pathogenic mutations are located at interaction sites involved in different steps of collagen VI assembly, from the trimeric-coiled coil region that mediates heterotrimerisation, to clusters of mutations in the triple-helical region involved in microfibril formation. Our microfibril structure provides a template for understanding supramolecular assembly, and offers a platform for rationale design of therapeutics for collagen VI pathologies.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62923-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62923-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62923-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().