Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase.

Sebastian Kalamajski, Dominique Bihan, Arkadiusz Bonna, Kristofer Rubin, Richard W Farndale

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

62 Citeringar (SciVal)

Sammanfattning

The hallmark of fibrotic disorders is a highly cross-linked and dense collagen matrix, a property driven by the oxidative action of lysyl oxidase. Other fibrosis-associated proteins also contribute to the final collagen matrix properties, one of which is fibromodulin - its interactions with collagen affect collagen cross-linking, packing, and fibril diameter. We investigated the possibility that a specific relationship exists between fibromodulin and lysyl oxidase, potentially imparting a specific collagen matrix phenotype. We mapped the fibromodulin-collagen interaction sites using the Collagen II and III Toolkit peptide libraries. Fibromodulin interacted with the peptides containing the known collagen cross-linking sites and the MMP-1 cleavage site in collagens I and II. Interestingly, the interaction sites are closely aligned within the quarter-staggered collagen fibril, suggesting a multivalent interaction between fibromodulin and several collagen helices. Furthermore, we detected an interaction between fibromodulin and lysyl oxidase - a major collagen cross-linking enzyme - and mapped the interaction site to 12 N-terminal amino acids on fibromodulin. This interaction also increases the activity of lysyl oxidase. Altogether, the data suggest a fibromodulin-modulated collagen cross-linking mechanism, where fibromodulin binds to a specific part of the collagen domain and also forms a complex together with lysyl oxidase, targeting the enzyme towards specific cross-linking sites.
Originalspråkengelska
Sidor (från-till)7951-79060
TidskriftJournal of Biological Chemistry
Volym291
Utgåva15
Tidigt onlinedatum2016 feb. 18
DOI
StatusPublished - 2016

Ämnesklassifikation (UKÄ)

  • Biokemi och molekylärbiologi

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