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The tyrosine sulfate rich domains of the LRR-proteins fibromodulin and osteoadherin bind motifs of basic clusters in a variety of heparin binding proteins including bioactive factors.

Tillgren, Viveka LU ; Önnerfjord, Patrik LU and Heinegård, Dick LU (2009) In Journal of Biological Chemistry Aug 21. p.28543-28553
Abstract
The small leucine-rich repeat proteins (SLRPs), fibromodulin and osteoadherin, have N-terminal extensions with a variable number of O-sulfated tyrosine residues. This modification combined with a number of aspartic and glutamic acid residues results in a highly negatively charged domain of less than 30 amino acids. We hypothesized that this domain shares functional properties with heparin regarding binding to proteins and polypeptides containing clusters of basic amino acids. Two other family members, PRELP and chondroadherin, have distinctly different clusters of basic amino acids in their N- and C-termini, respectively and PRELP is known to bind to heparin via this domain. Another heparin binding protein is the cytokine Oncostatin M,... (More)
The small leucine-rich repeat proteins (SLRPs), fibromodulin and osteoadherin, have N-terminal extensions with a variable number of O-sulfated tyrosine residues. This modification combined with a number of aspartic and glutamic acid residues results in a highly negatively charged domain of less than 30 amino acids. We hypothesized that this domain shares functional properties with heparin regarding binding to proteins and polypeptides containing clusters of basic amino acids. Two other family members, PRELP and chondroadherin, have distinctly different clusters of basic amino acids in their N- and C-termini, respectively and PRELP is known to bind to heparin via this domain. Another heparin binding protein is the cytokine Oncostatin M, with a different cluster of basic amino acids in its C-terminal. We used polypeptides representing these basic domains in solid phase assays and demonstrate interactions with the negatively charged N-terminal domain of fibromodulin and full length osteoadherin. The tyrosine sulfate domains also bound heparin binding proteins such as basic fibroblast growth factor (FGF-2), thrombospondin I (TSP-I), MMP 13, the NC4 domain of collagen IX and IL10. Fibronectin with large heparin binding domains did not bind, neither did CILP containing a heparin binding thrombospondin type I motif without clustered basic amino acids. Affinity depends on the number and position of the sulfated tyrosine residues shown by different binding properties of 10 kDa fragments subfractionated by ion exchange chromatography. These interactions may sequester growth factors, cytokines and MMPs in the extracellular matrix as well as contribute to its organization. (Less)
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published
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Journal of Biological Chemistry
volume
Aug 21
pages
28543 - 28553
publisher
ASBMB
external identifiers
  • wos:000270678900008
  • pmid:19700767
  • scopus:70350366783
  • pmid:19700767
ISSN
1083-351X
DOI
10.1074/jbc.M109.047076
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English
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yes
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The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Connective Tissue Biology (013230151)
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dbaaaa96-8609-4b99-8c3c-d8fbd3d1cc45 (old id 1469454)
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http://www.ncbi.nlm.nih.gov/pubmed/19700767?dopt=Abstract
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2016-04-04 07:07:29
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@article{dbaaaa96-8609-4b99-8c3c-d8fbd3d1cc45,
  abstract     = {The small leucine-rich repeat proteins (SLRPs), fibromodulin and osteoadherin, have N-terminal extensions with a variable number of O-sulfated tyrosine residues. This modification combined with a number of aspartic and glutamic acid residues results in a highly negatively charged domain of less than 30 amino acids. We hypothesized that this domain shares functional properties with heparin regarding binding to proteins and polypeptides containing clusters of basic amino acids. Two other family members, PRELP and chondroadherin, have distinctly different clusters of basic amino acids in their N- and C-termini, respectively and PRELP is known to bind to heparin via this domain. Another heparin binding protein is the cytokine Oncostatin M, with a different cluster of basic amino acids in its C-terminal. We used polypeptides representing these basic domains in solid phase assays and demonstrate interactions with the negatively charged N-terminal domain of fibromodulin and full length osteoadherin. The tyrosine sulfate domains also bound heparin binding proteins such as basic fibroblast growth factor (FGF-2), thrombospondin I (TSP-I), MMP 13, the NC4 domain of collagen IX and IL10. Fibronectin with large heparin binding domains did not bind, neither did CILP containing a heparin binding thrombospondin type I motif without clustered basic amino acids. Affinity depends on the number and position of the sulfated tyrosine residues shown by different binding properties of 10 kDa fragments subfractionated by ion exchange chromatography. These interactions may sequester growth factors, cytokines and MMPs in the extracellular matrix as well as contribute to its organization.},
  author       = {Tillgren, Viveka and Önnerfjord, Patrik and Heinegård, Dick},
  issn         = {1083-351X},
  language     = {eng},
  pages        = {28543--28553},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {The tyrosine sulfate rich domains of the LRR-proteins fibromodulin and osteoadherin bind motifs of basic clusters in a variety of heparin binding proteins including bioactive factors.},
  url          = {http://dx.doi.org/10.1074/jbc.M109.047076},
  doi          = {10.1074/jbc.M109.047076},
  volume       = {Aug 21},
  year         = {2009},
}