Structural analysis of collagen type I interactions with human fibronectin reveals a cooperative binding mode.

Journal article

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: Erat, M; Sladek, B; Campbell, I; Vakonakis, I

• Publication status: Published
• Journal: Journal of biological chemistry
• Volume: 288
• Issue: 24
• Pages: 17441-17450
• Publication date: 2013-06-01
• DOI: 10.1074/jbc.m113.469841
• EISSN: 1083-351X
• ISSN: 0021-9258
• Language: English
• Keywords: Amino Acid Sequence; Humans; Nuclear Magnetic Resonance, Biomolecular; Models, Molecular; Molecular Sequence Data; Solutions; Protein Binding; Hydrophobic and Hydrophilic Interactions; Collagen Type I; Fibronectins; Protein Structure, Quaternary; Tomography, X-Ray Computed; Protein Interaction Domains and Motifs; Protein Structure, Secondary; Protein Stability