Integrins are essential cell surface receptors with key roles in cell migration and adhesion. They are heterodimeric proteins made up of an alpha and a beta subunit, with each subunit comprised of a large extracellular domain, a single pass transmembrane helix and a short, largely unstructured cytoplasmic ‘tail’. Using NMR, we showed that the integrin activating protein talin binds to the membrane proximal region of the beta-integrin tail. The structure of this complex was solved using a chimeric integrin/PIP-kinase peptide, designed to boost the interaction affinity. Further investigations confirmed that the structure observed is also found with the native integrin peptide. Additional studies using NMR and liposomes, identified a cationic patch on the talin surface that interacts with the anionic lipid bilayer.
Binding of talin to both the membrane and the beta-integrin cytoplasmic tail, causes the beta-integrin transmembrane helix to separate from the alpha-subunit, leading to conformational rearrangement of the integrin extracellular domains, and subsequent ligand binding.