The NC4 domain of the cartilage-specific collagen IX inhibits complement directly due to attenuation of membrane attack formation and indirectly through binding and enhancing activity of complement inhibitors C4B-binding protein and factor H.
Kalchishkova, Nikolina LU ; Melin Fürst, Camilla LU ; Heinegård, Dick LU and Blom, Anna LU
(2011)
In Journal of Biological Chemistry
286(32).
p.27915-27926
- Abstract
- Collagen IX containing the N-terminal non-collagenous domain 4 (NC4) domain is unique to cartilage and a member of the family of fibril-associated collagens with both collagenous and non-collagenous domains. Collagen IX is located at the surface of fibrils formed by collagen II and a minor proportion of collagen XI, playing roles in tissue stability and integrity. The NC4 domain projects out from the fibril surface and provides sites for interaction with other matrix components such as cartilage oligomeric matrix protein (COMP), matrilins, fibromodulin and osteoadherin. Fragmentation of collagen IX and loss of the NC4 domain are early events in cartilage degradation in joint diseases that precedes major damage of collagen II fibrils. Our... (More)
- Collagen IX containing the N-terminal non-collagenous domain 4 (NC4) domain is unique to cartilage and a member of the family of fibril-associated collagens with both collagenous and non-collagenous domains. Collagen IX is located at the surface of fibrils formed by collagen II and a minor proportion of collagen XI, playing roles in tissue stability and integrity. The NC4 domain projects out from the fibril surface and provides sites for interaction with other matrix components such as cartilage oligomeric matrix protein (COMP), matrilins, fibromodulin and osteoadherin. Fragmentation of collagen IX and loss of the NC4 domain are early events in cartilage degradation in joint diseases that precedes major damage of collagen II fibrils. Our results demonstrate that NC4 can function as a novel inhibitor of the complement system able to bind C4, C3 and C9, and to directly inhibit C9 polymerisation and assembly of the lytic membrane attack complex. NC4 also binds the complement inhibitors C4b-binding protein and factor H and enhances their cofactor activity in degradation of activated complement components C4b and C3b. NC4 interactions with fibromodulin and osteoadherin inhibited binding to C1q and complement activation by these proteins. Taken together our results suggest that collagen IX and its interactions with matrix components is an important part of a machinery that protects the cartilage from complement activation and chronic inflammation seen in diseases like rheumatoid arthritis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2008235
- author
- Kalchishkova, Nikolina
LU
; Melin Fürst, Camilla
LU
; Heinegård, Dick
LU
and Blom, Anna
LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 286
- issue
- 32
- pages
- 27915 - 27926
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000293557800010
- pmid:21659506
- scopus:80051513019
- pmid:21659506
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M111.242834
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division III (013230700), Protein Chemistry (013017510), Connective Tissue Biology (013230151)
- id
- 2b423b13-ab9e-4978-989e-8f899f5996e0 (old id 2008235)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21659506?dopt=Abstract
- date added to LUP
- 2016-04-01 10:18:16
- date last changed
- 2022-04-12 04:58:54
@article{2b423b13-ab9e-4978-989e-8f899f5996e0,
abstract = {{Collagen IX containing the N-terminal non-collagenous domain 4 (NC4) domain is unique to cartilage and a member of the family of fibril-associated collagens with both collagenous and non-collagenous domains. Collagen IX is located at the surface of fibrils formed by collagen II and a minor proportion of collagen XI, playing roles in tissue stability and integrity. The NC4 domain projects out from the fibril surface and provides sites for interaction with other matrix components such as cartilage oligomeric matrix protein (COMP), matrilins, fibromodulin and osteoadherin. Fragmentation of collagen IX and loss of the NC4 domain are early events in cartilage degradation in joint diseases that precedes major damage of collagen II fibrils. Our results demonstrate that NC4 can function as a novel inhibitor of the complement system able to bind C4, C3 and C9, and to directly inhibit C9 polymerisation and assembly of the lytic membrane attack complex. NC4 also binds the complement inhibitors C4b-binding protein and factor H and enhances their cofactor activity in degradation of activated complement components C4b and C3b. NC4 interactions with fibromodulin and osteoadherin inhibited binding to C1q and complement activation by these proteins. Taken together our results suggest that collagen IX and its interactions with matrix components is an important part of a machinery that protects the cartilage from complement activation and chronic inflammation seen in diseases like rheumatoid arthritis.}},
author = {{Kalchishkova, Nikolina and Melin Fürst, Camilla and Heinegård, Dick and Blom, Anna}},
issn = {{1083-351X}},
language = {{eng}},
number = {{32}},
pages = {{27915--27926}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{The NC4 domain of the cartilage-specific collagen IX inhibits complement directly due to attenuation of membrane attack formation and indirectly through binding and enhancing activity of complement inhibitors C4B-binding protein and factor H.}},
url = {{http://dx.doi.org/10.1074/jbc.M111.242834}},
doi = {{10.1074/jbc.M111.242834}},
volume = {{286}},
year = {{2011}},
}