Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8825063
- author
- Kalamajski, Sebastian LU ; Bihan, Dominique ; Bonna, Arkadiusz ; Rubin, Kristofer LU and Farndale, Richard W
- organization
- publishing date
- 2016-02-18
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 291
- issue
- 15
- pages
- 7951 - 79060
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:26893379
- wos:000374056700017
- scopus:84964680239
- pmid:26893379
- 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
- 2016-04-04 07:03:12
- date last changed
- 2022-04-23 03:57:50
@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 = {{American Society for Biochemistry and Molecular Biology}},
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}},
doi = {{10.1074/jbc.M115.693408}},
volume = {{291}},
year = {{2016}},
}