The Concave Face of Decorin Mediates Reversible Dimerization and Collagen Binding |
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| Authors: | Mehwaesh Islam Jayesh Gor Stephen J Perkins Yoshihiro Ishikawa Hans Peter B?chinger Erhard Hohenester |
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| Institution: | From the ‡Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom.;§Department of Structural and Molecular Biology, University College London, London WC1E 6BT, United Kingdom.;¶Research Department, Shriners Hospital for Children, Portland, Oregon 97239, and ;‖Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239 |
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| 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. |
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| Keywords: | Collagen Extracellular Matrix Protein-Protein Interactions Proteoglycan Site-directed Mutagenesis |
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