Implications for Collagen Binding from the Crystallographic Structure of Fibronectin 6FnI1?C2FnII7FnI |
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| Authors: | Mich??le C Erat Ulrich Schwarz-Linek Andrew R Pickford Richard W Farndale Iain D Campbell and Ioannis Vakonakis |
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| Institution: | From the ‡Department of Biochemistry, University of Oxford, Oxford OX1 3QU, ;the §Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, Fife, KY16 9ST, Scotland, ;the ¶School of Biological Sciences, University of Portsmouth, Portsmouth PO1 2DY, and ;the ‖Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom |
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| Abstract: | Collagen and fibronectin (FN) are two abundant and essential components of the vertebrate extracellular matrix; they interact directly with cellular receptors and affect cell adhesion and migration. Past studies identified a FN fragment comprising six modules, 6FnI1–2FnII7–9FnI, and termed the gelatin binding domain (GBD) as responsible for collagen interaction. Recently, we showed that the GBD binds tightly to a specific site within type I collagen and determined the structure of domains 8–9FnI in complex with a peptide from that site. Here, we present the crystallographic structure of domains 6FnI1–2FnII7FnI, which form a compact, globular unit through interdomain interactions. Analysis of NMR titrations with single-stranded collagen peptides reveals a dominant collagen interaction surface on domains 2FnII and 7FnI; a similar surface appears involved in interactions with triple-helical peptides. Models of the complete GBD, based on the new structure and the 8–9FnI·collagen complex show a continuous putative collagen binding surface. We explore the implications of this model using long collagen peptides and discuss our findings in the context of FN interactions with collagen fibrils. |
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| Keywords: | Collagen Extracellular Matrix Proteins Fibronectin NMR Protein Structure X-ray Crystallography Gelatin Binding Domain Protein Interactions |
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