Fig. 2. The proposed domain structure and possible post-translational regulation of vinculin. (A) Scheme showing the primary structure of vinculin, annotated with the various binding domains and some secondary and tertiary structural information. Numbers near component boxes indicate the locations of specific binding sites along the polypeptide chain (starting from the N-terminus). (B) The regulation of vinculin-binding activities by conformational changes. The intramolecular interaction between the head and tail of vinculin leads to a ‘closed’ conformation and masks many of the binding sites. The interaction of vinculin with PtdIns(4,5)P₂ may release this inhibitory head-tail interaction and unmask different binding sites. (C) A hypothetical model for the effect of vinculin activation on the formation and assembly of focal contacts. Inactive vinculin (left) cannot crosslink the various molecular partners. Upon activation by PtdIns(4,5)P₂ (right), vinculin can bind to actin filaments and other focal contact components. Abbreviations: a, actin; F, FAK; I, integrins, pa, paxillin; r, profilin; t, talin; va, VASP; vi, vinculin.