title: The concave face of decorin mediates reversible dimerization and collagen binding.
abstract: Decorin, the prototypical small leucine-rich proteoglycan, binds to collagen and thereby regulates collagen assembly into fibrils. The crystal structure of the decorin core protein revealed a tight dimer formed by the association of two monomers via their concave faces (Scott, P. G., McEwan, P. A., Dodd, C. M., Bergmann, E. M., Bishop, P. N., and Bella, J. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 15633-15638). Whether decorin binds collagen as a dimer has been controversial. Using analytical ultracentrifugation, we determined a dissociation constant of 1.37 ± 0.30 μm for the mouse decorin dimer. Dimerization could be abolished by engineering glycosylation sites into the dimer interface; other interface mutants remained dimeric. The monomeric mutants were as stable as wild-type decorin in thermal unfolding experiments. Mutations on the concave face of decorin abolished collagen binding regardless of whether the mutant proteins retained the ability to dimerize or not. We conclude that the concave face of decorin mediates collagen binding and that the dimer therefore must dissociate to bind collagen.
authors.affiliation: From the Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Mehwaesh
authors.initials: M
authors.lastname: Islam
authors.forename: Jayesh
authors.initials: J
authors.lastname: Gor
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Perkins
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Bächinger
authors.forename: Erhard
authors.initials: E
authors.lastname: Hohenester
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D018360:Crystallography, X-Ray; D058575:Decorin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C546879:Dcn protein, mouse; D058575:Decorin; D011994:Recombinant Proteins; D003094:Collagen
keywords: Collagen; Extracellular Matrix; Protein-Protein Interactions; Proteoglycan; Site-directed Mutagenesis