A vinculin-binding domain from the talin rod unfolds to form a complex with the vinculin head
journal contributionposted on 10.12.2007, 10:26 by Ian Fillingham, Alexandre R. Gingras, Evangelos Papagrigoriou, Bipin Patel, Jonas Emsley, David R. Critchley, Gordon C.K. Roberts, Igor L. Barsukov
The cytoskeletal protein talin plays a key role in activating integrins and in coupling them to the actin cytoskeleton. Its N-terminal globular head, which binds β-integrins, is linked to an extended rod having a C-terminal actin-binding site and several vinculin-binding sites (VBSs). The NMR structure of residues 755-889 of the rod (containing a VBS) is shown to be an amphipathic 4-helix bundle with a left-handed topology. A talin peptide corresponding to the VBS binds the vinculin head; the X-ray crystallographic structure of this complex shows that the residues which interact with vinculin are buried in the hydrophobic core of the talin fragment. NMR shows that the interaction involves a major structural change in the talin fragment, including unfolding of one of its helices, making the VBS accessible to vinculin. Interestingly, the talin 755-889 fragment binds more than one vinculin head molecule, suggesting that the talin rod may contain additional as yet unrecognised VBSs.