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.
Highlights
The fibronectin (FN)-collagen interaction is important for cell adhesion and migration
The gelatin-binding domain” (GBD) Is an Elongated Monomer in Solution—Previously, NMR solution data indicated that FN modules do not undergo radical structural rearrangement in the complete GBD compared with its subfragments 6FnI1–2FnII7FnI and 8–9FnI [7, 26]
We have presented a model showing how the full-length GBD of FN and the most common collagen interact on a molecular scale
Summary
The fibronectin (FN)-collagen interaction is important for cell adhesion and migration. Results: FN modules 8–9FnI interact with two distinct sites in both chains of collagen I. All six collagen-binding FN modules interact cooperatively with a single collagen site. Collagen association with FN modules 8–9FnI 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 6FnI1–2FnII7FnI binds a specific collagen epitope next to the weakest 8–9FnI-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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
