Crystal structure of the vinculin tail suggests a pathway for activation

Vinculin plays a dynamic role in the assembly of the actin cytoskeleton. A strong interaction between its head and tail domains that regulates binding to other cytoskeletal components is disrupted by acidic phospholipids. Her e, we present the crystal structure of the vinculin tail, residues 879-1066 . Five amphipathic helices form an antiparallel bundle that resembles excha ngeable apolipoproteins. A C-terminal arm wraps across the base of the bund le and emerges as a hydrophobic hairpin surrounded by a collar of basic res idues, adjacent to the N terminus. We show that the C-terminal arm is requi red for binding to acidic phospholipids but not to actin, and that binding either ligand induces conformational changes that may represent the first s tep in activation.