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

Research output: Contribution to journalArticle


title = "Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase.",
abstract = "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.",
author = "Sebastian Kalamajski and Dominique Bihan and Arkadiusz Bonna and Kristofer Rubin and Farndale, {Richard W}",
year = "2016",
doi = "10.1074/jbc.M115.693408",
language = "English",
volume = "291",
pages = "7951--79060",
journal = "Journal of Biological Chemistry",
issn = "1083-351X",
publisher = "ASBMB",
number = "15",