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A minimized human integrin alpha(5)beta(1) that retains ligand recognition
J L Banères1, F Roquet, A Martin
1Chimie Biomoléculaire et Interactions Biologiques, UPRESA CNRS 5074, Faculté de Pharmacie, 15 Av. Ch. Flahault, 34060 Montpellier Cédex 2, France. baneres@pharma.univ-montp1.fr
The Journal of Biological Chemistry
|February 22, 2000
Summary
Human integrin alpha(5)beta(1) mini-integrin fragments bind fibronectin. Divalent cations like Mg(2+) induce conformational changes, enabling RGD-dependent ligand recognition and a two-site binding model.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Cell Biology
Background:
- Integrins are crucial cell surface receptors mediating cell adhesion.
- The alpha(5)beta(1) integrin specifically binds fibronectin via an RGD sequence.
- Understanding integrin structure-function relationships is key to cell signaling research.
Purpose of the Study:
- To structurally characterize isolated human integrin alpha(5)beta(1) fragments.
- To investigate the role of divalent cations in integrin-beta(1) and integrin-alpha(5) function.
- To elucidate the mechanism of fibronectin binding and conformational changes.
Main Methods:
- Circular dichroism (CD) spectroscopy to determine structural integrity and conformational changes.
- Water Nuclear Magnetic Resonance (NMR) relaxation to assess metal ion hydration.
- Recombinant protein expression and purification for structural and binding studies.
- Use of RGD mimetics to probe binding interactions.
Main Results:
- Isolated alpha(5) and beta(1) integrin fragments were structurally defined in solution.
- Divalent cations (Ca(2+), Mg(2+), Mn(2+)) induced distinct conformational adaptations in alpha(5) and beta(1) fragments.
- Both fragments formed a stable alpha(5)beta(1) mini-integrin, binding fibronectin in an RGD-dependent manner.
- Fibronectin ligand binding induced conformational changes in the ligand and displaced metal ions from beta(1).
Conclusions:
- The alpha(5)beta(1) mini-integrin retains RGD-dependent fibronectin recognition.
- Divalent cations play critical roles in modulating integrin conformation and ligand binding.
- A two-site model for RGD binding to both alpha and beta integrin subunits is proposed.
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