The Tyrosine Sulfate Domain of Fibromodulin Binds Collagen and Enhances Fibril Formation
Tillgren, Viveka LU ; Mörgelin, Matthias LU ; Önnerfjord, Patrik LU
; Kalamajski, Sebastian
LU
and Aspberg, Anders
LU
(2016)
In Journal of Biological Chemistry
291(45).
p.23744-23755
- Abstract
Small leucine-rich proteoglycans interact with other extracellular matrix proteins and are important regulators of matrix assembly. Fibromodulin has a key role in connective tissues, binding collagen through two identified binding sites in its leucine-rich repeat domain and regulating collagen fibril formation in vitro and in vivo Some nine tyrosine residues in the fibromodulin N-terminal domain are O-sulfated, a posttranslational modification often involved in protein interactions. The N-terminal domain mimics heparin, binding proteins with clustered basic amino acid residues. Because heparin affects collagen fibril formation, we investigated whether tyrosine sulfate is involved in fibromodulin interactions with collagen. Using... (More)
Small leucine-rich proteoglycans interact with other extracellular matrix proteins and are important regulators of matrix assembly. Fibromodulin has a key role in connective tissues, binding collagen through two identified binding sites in its leucine-rich repeat domain and regulating collagen fibril formation in vitro and in vivo Some nine tyrosine residues in the fibromodulin N-terminal domain are O-sulfated, a posttranslational modification often involved in protein interactions. The N-terminal domain mimics heparin, binding proteins with clustered basic amino acid residues. Because heparin affects collagen fibril formation, we investigated whether tyrosine sulfate is involved in fibromodulin interactions with collagen. Using full-length fibromodulin and its N-terminal tyrosine-sulfated domain purified from tissue, as well as recombinant fibromodulin fragments, we found that the N-terminal domain binds collagen. The tyrosine-sulfated domain and the leucine-rich repeat domain both bound to three specific sites along the collagen type I molecule, at the N terminus and at 100 and 220 nm from the N terminus. The N-terminal domain shortened the collagen fibril formation lag phase and tyrosine sulfation was required for this effect. The isolated leucine-rich repeat domain inhibited the fibril formation rate, and full-length fibromodulin showed a combination of these effects. The fibrils formed in the presence of fibromodulin or its fragments showed more organized structure. Fibromodulin and its tyrosine sulfate domain remained bound on the formed fiber. Taken together, this suggests a novel, regulatory function for tyrosine sulfation in collagen interaction and control of fibril formation.
(Less)
- author
- Tillgren, Viveka
LU
; Mörgelin, Matthias
LU
; Önnerfjord, Patrik
LU
; Kalamajski, Sebastian
LU
and Aspberg, Anders
LU
- organization
- publishing date
- 2016-11-04
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 291
- issue
- 45
- pages
- 12 pages
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- scopus:84994338579
- wos:000387884400034
- pmid:27634037
- ISSN
- 0021-9258
- DOI
- 10.1074/jbc.M116.730325
- language
- English
- LU publication?
- yes
- id
- 969dc349-c9a4-4bc8-9d7f-22afd33d02da
- date added to LUP
- 2016-11-30 13:19:28
- date last changed
- 2024-05-03 14:56:31
@article{969dc349-c9a4-4bc8-9d7f-22afd33d02da,
abstract = {{<p>Small leucine-rich proteoglycans interact with other extracellular matrix proteins and are important regulators of matrix assembly. Fibromodulin has a key role in connective tissues, binding collagen through two identified binding sites in its leucine-rich repeat domain and regulating collagen fibril formation in vitro and in vivo Some nine tyrosine residues in the fibromodulin N-terminal domain are O-sulfated, a posttranslational modification often involved in protein interactions. The N-terminal domain mimics heparin, binding proteins with clustered basic amino acid residues. Because heparin affects collagen fibril formation, we investigated whether tyrosine sulfate is involved in fibromodulin interactions with collagen. Using full-length fibromodulin and its N-terminal tyrosine-sulfated domain purified from tissue, as well as recombinant fibromodulin fragments, we found that the N-terminal domain binds collagen. The tyrosine-sulfated domain and the leucine-rich repeat domain both bound to three specific sites along the collagen type I molecule, at the N terminus and at 100 and 220 nm from the N terminus. The N-terminal domain shortened the collagen fibril formation lag phase and tyrosine sulfation was required for this effect. The isolated leucine-rich repeat domain inhibited the fibril formation rate, and full-length fibromodulin showed a combination of these effects. The fibrils formed in the presence of fibromodulin or its fragments showed more organized structure. Fibromodulin and its tyrosine sulfate domain remained bound on the formed fiber. Taken together, this suggests a novel, regulatory function for tyrosine sulfation in collagen interaction and control of fibril formation.</p>}},
author = {{Tillgren, Viveka and Mörgelin, Matthias and Önnerfjord, Patrik and Kalamajski, Sebastian and Aspberg, Anders}},
issn = {{0021-9258}},
language = {{eng}},
month = {{11}},
number = {{45}},
pages = {{23744--23755}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{The Tyrosine Sulfate Domain of Fibromodulin Binds Collagen and Enhances Fibril Formation}},
url = {{http://dx.doi.org/10.1074/jbc.M116.730325}},
doi = {{10.1074/jbc.M116.730325}},
volume = {{291}},
year = {{2016}},
}