Structure of integrin 5 1 in complex with fibronectin
Open Access
- 15 September 2003
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 22 (18), 4607-4615
- https://doi.org/10.1093/emboj/cdg445
Abstract
The membrane‐distal headpiece of integrins has evolved to specifically bind large extracellular protein ligands, but the molecular architecture of the resulting complexes has not been determined. We used molecular electron microscopy to determine the three‐dimensional structure of the ligand‐binding headpiece of integrin α5β1 complexed with fragments of its physiological ligand fibronectin. The density map for the unliganded α5β1 headpiece shows a ‘closed’ conformation similar to that seen in the αVβ3 crystal structure. By contrast, binding to fibronectin induces an ‘open’ conformation with a dramatic, ∼80° change in the angle of the hybrid domain of the β subunit relative to its I‐like domain. The fibronectin fragment binds to the interface between the β‐propeller and I‐like domains in the integrin headpiece through the RGD‐containing module 10, but direct contact of the synergy‐region‐containing module 9 to integrin is not evident. This finding is corroborated by kinetic analysis of real‐time binding data, which shows that the synergy site greatly enhances kon but has little effect on the stability or koff of the complex.Keywords
This publication has 44 references indexed in Scilit:
- Structures of the αL I Domain and Its Complex with ICAM-1 Reveal a Shape-Shifting Pathway for Integrin RegulationCell, 2003
- IntegrinsCell, 2002
- The Role of the Specificity-Determining Loop of the Integrin β Subunit I-like Domain in Autonomous Expression, Association with the α Subunit, and Ligand BindingBiochemistry, 2002
- Molecular Basis of Ligand Recognition by Integrin α5β1Published by Elsevier BV ,2000
- Defining Fibronectin's Cell Adhesion Synergy Site by Site-Directed MutagenesisThe Journal of cell biology, 2000
- Fine mapping of inhibitory anti-α5 monoclonal antibody epitopes that differentially affect integrin‒ligand bindingBiochemical Journal, 1999
- Solution structure and dynamics of linked cell attachment modules of mouse fibronectin containing the RGD and synergy regions: comparison with the human fibronectin crystal structureJournal of Molecular Biology, 1998
- SPIDER and WEB: Processing and Visualization of Images in 3D Electron Microscopy and Related FieldsJournal of Structural Biology, 1996
- Comparison of a Structural and a Functional EpitopeJournal of Molecular Biology, 1993
- Proton NMR assignment and secondary structure of the cell adhesion type III module of fibronectinBiochemistry, 1992