Repository logo

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

Published version

Repository DOI

Change log


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


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. Together, 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 with lysyl oxidase, targeting the enzyme toward specific cross-linking sites.



collagen, cross-linking, extracellular matrix, fibromodulin, lysyl oxidase, small leucine-rich proteoglycan (SLRP), Amino Acid Sequence, Animals, Binding Sites, Cell Line, Collagen, Enzyme Activation, Extracellular Matrix Proteins, Fibromodulin, Gene Deletion, Humans, Mice, Mice, Knockout, Molecular Sequence Data, Protein Interaction Maps, Protein-Lysine 6-Oxidase, Proteoglycans

Journal Title

J Biol Chem

Conference Name

Journal ISSN


Volume Title



Elsevier BV
Wellcome Trust (094470/Z/10/Z)
Medical Research Council (G0400701)
British Heart Foundation (RG/15/4/31268)
British Heart Foundation (None)
SK and KR were supported by grants from the Swedish Cancer Foundation, the Swedish Research Council, the Alfred Österlund Foundation, the Crafoord Foundation, the Magnus Bergvall Foundation, and the Åke Wiberg Foundation; AB, DB and RWF by grants from the Wellcome Trust (094470/Z/10/Z) and British Heart Foundation (RG/15/4/31268).