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

Kalamajski, Sebastian LU ; Bihan, Dominique; Bonna, Arkadiusz; Rubin, Kristofer LU and Farndale, Richard W (2016) In Journal of Biological Chemistry 291(15). p.7951-79060
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
291
issue
15
pages
7951 - 79060
publisher
ASBMB
external identifiers
  • pmid:26893379
  • wos:000374056700017
  • scopus:84964680239
ISSN
1083-351X
DOI
10.1074/jbc.M115.693408
language
English
LU publication?
yes
id
8233d566-ac64-4e2b-89a5-ef320ec420ec (old id 8825063)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26893379?dopt=Abstract
date added to LUP
2016-03-03 12:01:45
date last changed
2017-11-19 04:16:14
@article{8233d566-ac64-4e2b-89a5-ef320ec420ec,
  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       = {Kalamajski, Sebastian and Bihan, Dominique and Bonna, Arkadiusz and Rubin, Kristofer and Farndale, Richard W},
  issn         = {1083-351X},
  language     = {eng},
  month        = {02},
  number       = {15},
  pages        = {7951--79060},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase.},
  url          = {http://dx.doi.org/10.1074/jbc.M115.693408},
  volume       = {291},
  year         = {2016},
}