Details

Autor(en) / Beteiligte

• Liddington, Robert C
• Bakolitsa, Constantina
• Cohen, Daniel M
• Bankston, Laurie A
• Bobkov, Andrey A
• Cadwell, Gregory W
• Jennings, Lisa
• Critchley, David R
• Craig, Susan W

Titel

Structural basis for vinculin activation at sites of cell adhesion

Ist Teil von

• Nature, 2004-07, Vol.430 (6999), p.583-586

Ort / Verlag

London: Nature Publishing

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• Vinculin is a highly conserved intracellular protein with a crucial role in the maintenance and regulation of cell adhesion and migration. In the cytosol, vinculin adopts a default autoinhibited conformation. On recruitment to cell-cell and cell-matrix adherens-type junctions, vinculin becomes activated and mediates various protein-protein interactions that regulate the links between F-actin and the cadherin and integrin families of cell-adhesion molecules. Here we describe the crystal structure of the full-length vinculin molecule (1,066 amino acids), which shows a five-domain autoinhibited conformation in which the carboxy-terminal tail domain is held pincer-like by the vinculin head, and ligand binding is regulated both sterically and allosterically. We show that conformational changes in the head, tail and proline-rich domains are linked structurally and thermodynamically, and propose a combinatorial pathway to activation that ensures that vinculin is activated only at sites of cell adhesion when two or more of its binding partners are brought into apposition.