The Interaction of Vinculin with Actin
Figure 8
Formation of a vinculin open II conformation.
In its closed conformation (A) vinculin is not likely to bind actin filament. Separation of D1 from Vt constitutes formation of the open I conformation (B) and molecular dynamics simulations suggest the open I conformation can bind along the actin filament. Another critical link between Vt and the vinculin head domains exists at the interface between D4 and Vt. Separation of Vt from D4 results in formation of an open 2 conformation (C). (D) When the open II conformation is equilibrated after being formed D1 moves towards Vt and the loop region reduces its strain. However, Vt remains detached from the vinculin head and D1 remains removed from Vt. In this open II conformation vinculin could interact with F-actin both along the filament and at its barbed-end. Using the umbrella sampling method [79] the potential of mean force for two reaction coordinates were calculated: (E) the distance between D1 and Vt, and (F) the distance between D4 and Vt. Progress along reaction coordinate (E) leads to formation of the open I conformation. Progress along reaction coordinate (F) leads to formation of the open II conformation. Formation of the open I conformation has a free energy barrier of 90 KT and the open I conformation is not likely to stay open without persistent energy input. The formation of the open II conformation following formation of the open I conformation has a smaller free energy barrier of less than 20 KT. The plateau at the end of reaction coordinate (F) suggests the open II conformation could remain open without external force.