| First Author | Papagrigoriou E | Year | 2004 |
| Journal | EMBO J | Volume | 23 |
| Issue | 15 | Pages | 2942-51 |
| PubMed ID | 15272303 | Mgi Jnum | J:116247 |
| Mgi Id | MGI:3693386 | Doi | 10.1038/sj.emboj.7600285 |
| Citation | Papagrigoriou E, et al. (2004) Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle. EMBO J 23(15):2942-51 |
| abstractText | The interaction between the cytoskeletal proteins talin and vinculin plays a key role in integrin-mediated cell adhesion and migration. We have determined the crystal structures of two domains from the talin rod spanning residues 482-789. Talin 482-655, which contains a vinculin-binding site (VBS), folds into a five-helix bundle whereas talin 656-789 is a four-helix bundle. We show that the VBS is composed of a hydrophobic surface spanning five turns of helix 4. All the key side chains from the VBS are buried and contribute to the hydrophobic core of the talin 482-655 fold. We demonstrate that the talin 482-655 five-helix bundle represents an inactive conformation, and mutations that disrupt the hydrophobic core or deletion of helix 5 are required to induce an active conformation in which the VBS is exposed. We also report the crystal structure of the N-terminal vinculin head domain in complex with an activated form of talin. Activation of the VBS in talin and the recruitment of vinculin may support the maturation of small integrin/talin complexes into more stable adhesions. |
