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Integrins are cell surface receptors crucial for cell migration and adhesion. They are activated by interactions of the talin head domain with the membrane surface and the integrin β cytoplasmic tail. Here, we use coarse-grained molecular dynamic simulations and nuclear magnetic resonance spectroscopy to elucidate the membrane-binding surfaces of the talin head (F2-F3) domain. In particular, we show that mutations in the four basic residues (K258E, K274E, R276E, and K280E) in the F2 binding surface reduce the affinity of the F2-F3 for the membrane and modify its orientation relative to the bilayer. Our results highlight the key role of anionic lipids in talin/membrane interactions. Simulation of the F2-F3 in complex with the α/β transmembrane dimer reveals information for its orientation relative to the membrane. Our studies suggest that the perturbed orientation of talin relative to the membrane in the F2 mutant would be expected to in turn perturb talin/integrin interactions.

Original publication

DOI

10.1016/j.str.2010.07.012

Type

Journal article

Journal

Structure

Publication Date

13/10/2010

Volume

18

Pages

1280 - 1288

Keywords

Amino Acid Sequence, Animals, Antigens, CD29, Binding Sites, Humans, Lipid Bilayers, Magnetic Resonance Spectroscopy, Membrane Lipids, Models, Molecular, Molecular Dynamics Simulation, Molecular Sequence Data, Multiprotein Complexes, Mutation, Platelet Membrane Glycoprotein IIb, Protein Binding, Protein Multimerization, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Talin