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Integrins are heterodimeric (αβ) cell surface receptors that are potential therapeutic targets for a number of diseases. Despite the existence of structural data for all parts of integrins, the structure of the complete integrin receptor is still not available. We have used available structural data to construct a model of the complete integrin receptor in complex with talin F2-F3 domain. It has been shown that the interactions of integrins with their lipid environment are crucial for their function but details of the integrin/lipid interactions remain elusive. In this study an integrin/talin complex was inserted in biologically relevant bilayers that resemble the cell plasma membrane containing zwitterionic and charged phospholipids, cholesterol and sphingolipids to study the dynamics of the integrin receptor and its effect on bilayer structure and dynamics. The results of this study demonstrate the dynamic nature of the integrin receptor and suggest that the presence of the integrin receptor alters the lipid organization between the two leaflets of the bilayer. In particular, our results suggest elevated density of cholesterol and of phosphatidylserine lipids around the integrin/talin complex and a slowing down of lipids in an annulus of ~30 Å around the protein due to interactions between the lipids and the integrin/talin F2-F3 complex. This may in part regulate the interactions of integrins with other related proteins or integrin clustering thus facilitating signal transduction across cell membranes.

Original publication

DOI

10.1007/s00232-016-9908-z

Type

Journal article

Journal

J Membr Biol

Publication Date

08/2017

Volume

250

Pages

337 - 351

Keywords

Integrin, Lipid diffusion, Molecular dynamics simulations, Talin, Amino Acid Motifs, Binding Sites, Cholesterol, Humans, Integrin alphaVbeta3, Lipid Bilayers, Molecular Dynamics Simulation, Phosphatidylcholines, Phosphatidylethanolamines, Phosphatidylserines, Platelet Glycoprotein GPIIb-IIIa Complex, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Protein Multimerization, Protein Structure, Tertiary, Protein Subunits, Sequence Homology, Amino Acid, Talin, Thermodynamics