The Structure of the Talin/Integrin Complex at a Lipid Bilayer: An NMR and MD Simulation Study
| Autor: | Mark S.P. Sansom, Iain D. Campbell, Benjamin T. Goult, Nicholas J. Anthis, Kate L. Wegener, Antreas C. Kalli |
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| Rok vydání: | 2010 |
| Předmět: |
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Molecular Platelet Membrane Glycoprotein IIb Talin Magnetic Resonance Spectroscopy Membrane lipids Lipid Bilayers Molecular Sequence Data Integrin macromolecular substances Molecular Dynamics Simulation Biology Article Membrane Lipids 03 medical and health sciences 0302 clinical medicine Protein structure Structural Biology Integrin complex Animals Humans Amino Acid Sequence Lipid bilayer Molecular Biology 030304 developmental biology 0303 health sciences Binding Sites Sequence Homology Amino Acid Integrin beta1 Bilayer Transmembrane protein Protein Structure Tertiary 3. Good health Cell biology Multiprotein Complexes Mutation biology.protein Protein Multimerization 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Structure(London, England:1993) |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/j.str.2010.07.012 |
| Popis: | Summary 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. Graphical Abstract Highlights ► Simulations and NMR define the interactions of the talin head domain with membranes ► Talin binds to anionic lipids in a bilayer via the F2 subdomain ► Mutations in the F2 lipid-binding site may perturb talin/integrin interactions |
| Databáze: | OpenAIRE |
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