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

J Biol Chem. 2009 Oct 16;284(42):28543-53. doi: 10.1074/jbc.M109.047076. Epub 2009 Aug 21.

Abstract

The small leucine-rich repeat proteins, 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 terminus. 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-2, thrombospondin I, MMP13, the NC4 domain of collagen IX, and interleukin-10. 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 matrix metalloproteinases in the extracellular matrix as well as contribute to its organization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acids / chemistry
  • Animals
  • Antimicrobial Cationic Peptides / chemistry*
  • Blood Proteins / chemistry*
  • Carrier Proteins / chemistry*
  • Cattle
  • Collagen / chemistry
  • Extracellular Matrix Proteins / chemistry*
  • Fibromodulin
  • Humans
  • Oncostatin M / chemistry
  • Peptides / chemistry
  • Protein Binding
  • Protein Structure, Tertiary
  • Proteoglycans / chemistry*
  • Sulfates / chemistry
  • Tyrosine / chemistry*

Substances

  • AZU1 protein, human
  • Amino Acids
  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Carrier Proteins
  • Extracellular Matrix Proteins
  • FMOD protein, human
  • Peptides
  • Proteoglycans
  • Sulfates
  • osteoadherin
  • Oncostatin M
  • Fibromodulin
  • Tyrosine
  • Collagen