Homologous sequence in lumican and fibromodulin leucine-rich repeat 5-7 competes for collagen binding.
Lumican and fibromodulin compete for collagen type I binding in vitro, and fibromodulin-deficient mice have 4-fold more lumican in tendons. These observations indicate that homologous sequences in lumican and fibromodulin bind to collagen type I. Here, we demonstrate that lumican binding to collagen type I is mediated mainly by Asp-213 in leucine-rich repeat (LRR) 7. The mutation D213N in lumican impairs interaction with collagen, and the lumican fragment spanning LRRs 5-7 is an efficient inhibitor of collagen binding. Also, the lumican LRR 7 sequence-based synthetic peptide CYLDNNKC inhibits the binding to collagen. Homologous collagen-binding site in fibromodulin, located in LRRs 5-7, inhibits the binding of lumican to collagen, and the mutation E251Q in this fibromodulin fragment does not inhibit the lumican-collagen binding. Lumican, but not the D213N mutation, lowers the melting point and affects the packing of collagen fibrils.
Kalamajski
Sebastian
S
Department of Experimental Medical Science, University of Lund, SE-221 84 Lund, Sweden. Electronic address: Sebastian.Kalamajski@med.lu.se.
Oldberg
Åke
Å
Department of Experimental Medical Science, University of Lund, SE-221 84 Lund, Sweden.
D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D024042:Collagen Type I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000071235:Fibromodulin; D006801:Humans; D007632:Keratan Sulfate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000071234:Lumican; D051379:Mice; D020125:Mutation, Missense; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011509:Proteoglycans / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D011508:Chondroitin Sulfate Proteoglycans; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; C000604332:Fmod protein, mouse; C000604306:LUM protein, human; C000604307:Lum protein, mouse; D000071234:Lumican; D010455:Peptides; D011509:Proteoglycans; D000071235:Fibromodulin; D007632:Keratan Sulfate