Figure 6.

A mechanism for vinculin activation: VBS linking followed by binding. Simulation of VBS interaction with autoinhibited vinculin suggests that VBS can link to D1 but cannot insert into D1 with Vt in close proximity. Simulation of VBS interaction with activated vinculin suggests that VBS can link to and insert into D1 after the proximity of Vt is removed. Together, these results suggest the following mechanism for vinculin activation: (I) lower-VBS links to D1; (II) vinculin is stretched (by simultaneous interaction with talin and actin perhaps); and (III) VBS fully inserts into D1.