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Structure of integrin alpha5beta1 in complex with fibronectin
Junichi Takagi1, Konstantin Strokovich, Timothy A Springer
1The Center for Blood Research, Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. takagi@protein.osaka-u.ac.jp
The EMBO Journal
|September 13, 2003
Summary
Integrin alpha5beta1 binds fibronectin by opening its structure, revealing how these cell adhesion molecules interact with extracellular proteins like fibronectin.
Area of Science:
- Biochemistry
- Structural Biology
- Cell Biology
Background:
- Integrins are crucial cell surface receptors that mediate cell adhesion to the extracellular matrix.
- The ligand-binding headpiece of integrins interacts with large extracellular proteins, but its structural complexes are not well understood.
Purpose of the Study:
- To determine the three-dimensional structure of the integrin alpha5beta1 headpiece bound to fibronectin fragments.
- To elucidate the molecular architecture of the integrin-ligand complex.
Main Methods:
- Molecular electron microscopy (cryo-EM) was used to visualize the integrin-fibronectin complex.
- Kinetic analysis of real-time binding data was employed to study binding dynamics.
Main Results:
- The unliganded integrin alpha5beta1 headpiece adopts a 'closed' conformation.
- Fibronectin binding induces an 'open' conformation in integrin alpha5beta1, with an ~80-degree change in the beta subunit's hybrid domain.
- Fibronectin module 10 binds the integrin headpiece, while module 9 does not directly contact the integrin.
Conclusions:
- Ligand binding induces significant conformational changes in integrin alpha5beta1.
- The RGD-containing fibronectin module 10 is key for integrin binding, while the synergy site (module 9) modulates binding kinetics.
- Structural insights into integrin-fibronectin interactions provide a basis for understanding cell adhesion mechanisms.