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Sebastian Kalamajski

Assistant researcher

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

Author

  • Viveka Tillgren
  • Matthias Mörgelin
  • Patrik Önnerfjord
  • Sebastian Kalamajski
  • Anders Aspberg

Summary, in English

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.

Department/s

  • Rheumatology
  • Infection Medicine (BMC)
  • Molecular Skeletal Biology

Publishing year

2016-11-04

Language

English

Pages

23744-23755

Publication/Series

Journal of Biological Chemistry

Volume

291

Issue

45

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Other Basic Medicine

Status

Published

Research group

  • Molecular Skeletal Biology

ISBN/ISSN/Other

  • ISSN: 0021-9258