title: Structural analysis of collagen type I interactions with human fibronectin reveals a cooperative binding mode.
abstract: Despite its biological importance, the interaction between fibronectin (FN) and collagen, two abundant and crucial tissue components, has not been well characterized on a structural level. Here, we analyzed the four interactions formed between epitopes of collagen type I and the collagen-binding fragment (gelatin-binding domain (GBD)) of human FN using solution NMR, fluorescence, and small angle x-ray scattering methods. Collagen association with FN modules (8-9)FnI occurs through a conserved structural mechanism but exhibits a 400-fold disparity in affinity between collagen sites. This disparity is reduced in the full-length GBD, as (6)FnI(1-2)FnII(7)FnI binds a specific collagen epitope next to the weakest (8-9)FnI-binding site. The cooperative engagement of all GBD modules with collagen results in four broadly equipotent FN-collagen interaction sites. Collagen association stabilizes a distinct monomeric GBD conformation in solution, giving further evidence to the view that FN fragments form well defined functional and structural units.
authors: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom.
authors: Michèle C
authors: MC
authors: Erat
authors: Barbara
authors: B
authors: Sladek
authors: Iain D
authors: ID
authors: Campbell
authors: Ioannis
authors: I
authors: Vakonakis
mesh_terms: D000595:Amino Acid Sequence; D024042:Collagen Type I / Q000737:chemistry*; D005353:Fibronectins / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D012996:Solutions; D014057:Tomography, X-Ray Computed
chemical_list: D024042:Collagen Type I; D005353:Fibronectins; D012996:Solutions
keywords: Collagen; Extracellular Matrix Proteins; Fibronectin; GBD; NMR; SAXS; X-ray Crystallography
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