The Tyrosine Sulfate Domain of Fibromodulin Binds Collagen and Enhances Fibril Formation

Tillgren et al., Journal of biological Chemistry (2016) - PMID: 27634037

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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 collagenfibrilformation 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. Since heparin affects collagenfibrilformation, we investigated whether tyrosinesulfate 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 domainbindscollagen. 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 nm and 220 nm from the N-terminus. The N-terminal domain shortened the collagenfibrilformation lag phase and tyrosine sulfation was required for this effect. The isolated leucine rich repeat domain inhibited the fibrilformation 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 tyrosinesulfatedomain remained bound on the formed fiber. Taken together, this suggests a novel, regulatory function for tyrosine sulfation in collagen interaction and control of fibrilformation.

Copyright © 2016, The American Society for Biochemistry and Molecular Biology.


collagen; extracellular matrix; fibrillogenesis; fibromodulin; post-translational modification (PTM); protein assembly; tyrosine sulfation

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