Fibromodulin binds collagen type I via Glu-353 and Lys-355 in leucine-rich repeat 11.
Fibromodulin belongs to the small leucine-rich repeat proteoglycan family, interacts with collagen type I, and controls collagen fibrillogenesis and assembly. Here, we show that a major fibromodulin-binding site for collagen type I is located in leucine-rich repeat 11 in the C terminus of the leucine-rich repeat domain. We identified Glu-353 and Lys-355 in repeat 11 as essential for binding, and the synthetic peptide RLDGNEIKR, including Glu-353 and Lys-355, inhibits the binding of fibromodulin to collagen in vitro. Fibromodulin and lumican compete for the same binding region on collagen, and fibromodulin can inhibit the binding of lumican to collagen type I. However, the peptide RLDGNEIKR does not inhibit the binding of lumican to collagen, suggesting separate but closely situated fibromodulin- and lumican-binding sites in collagen. The collagen-binding Glu-353 and Lys-355 residues in fibromodulin are exposed on the exterior of the beta-sheet-loop structure of the leucine-rich repeat, which resembles the location of interacting residues in other leucine-rich repeat proteins, e.g. decorin.
Kalamajski
Sebastian
S
Department of Experimental Medical Science, University of Lund, SE-221 84 Lund, Sweden.
Oldberg
Åke
Å
Department of Experimental Medical Science, University of Lund, SE-221 84 Lund, Sweden. Electronic address: Ake.Oldberg@med.lu.se.
D001665:Binding Sites; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism; D024042:Collagen Type I / Q000737:chemistry* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000378:metabolism; D000071235:Fibromodulin; D018698:Glutamic Acid; D006801:Humans; D007632:Keratan Sulfate / Q000737:chemistry / Q000378:metabolism; D000090263:Leucine-Rich Repeat Proteins; D000071234:Lumican; D008239:Lysine; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D011509:Proteoglycans / Q000737:chemistry* / Q000378:metabolism
D011508:Chondroitin Sulfate Proteoglycans; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; C000604306:LUM protein, human; D000090263:Leucine-Rich Repeat Proteins; D000071234:Lumican; D011506:Proteins; D011509:Proteoglycans; D000071235:Fibromodulin; D018698:Glutamic Acid; D007632:Keratan Sulfate; D008239:Lysine