Figure 2.

Suggested models of vinculin activation in the cell. Two competing hypotheses regarding the method of vinculin activation have been presented. (A) Simultaneous interaction of actin and talin with the two binding sites on vinculin would induce activation, possibly through a stretching force. (B) Talin VBS interacts with vinculin via a helical bundle conversion mechanism. Subsequently, vinculin is activated and its Vt domain can then interact with actin. MD is used to simulate conformational changes due to stretching of vinculin as suggested by the simultaneous interaction hypothesis, and to simulate conformational changes due to helical bundle conversion. The two sets of simulations are compared to see which is consistent with the structural changes needed for vinculin activation.