The structure of the talin/integrin complex at a lipid bilayer: an NMR and MD simulation study.

Kalli, Antreas C ORCID: 0000-0001-7156-9403, Wegener, Kate L, Goult, Benjamin T ORCID: 0000-0002-3438-2807, Anthis, Nicholas J ORCID: 0000-0002-1881-450X, Campbell, Iain D and Sansom, Mark SP ORCID: 0000-0001-6360-7959 (2010) The structure of the talin/integrin complex at a lipid bilayer: an NMR and MD simulation study. Structure (London, England : 1993), 18 (10). pp. 1280-1288.

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Official URL: http://dx.doi.org/10.1016/j.str.2010.07.012

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Animals, Humans, Multiprotein Complexes, Membrane Lipids, Lipid Bilayers, Talin, Platelet Membrane Glycoprotein IIb, Magnetic Resonance Spectroscopy, Binding Sites, Amino Acid Sequence, Protein Structure, Tertiary, Protein Binding, Sequence Homology, Amino Acid, Mutation, Models, Molecular, Molecular Sequence Data, Protein Multimerization, Molecular Dynamics Simulation, Integrin beta1
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	13 Mar 2024 09:50
Last Modified:	13 Mar 2024 09:50
DOI:	10.1016/j.str.2010.07.012
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179329