How Force Might Activate Talin's Vinculin Binding Sites: SMD Reveals a Structural Mechanism
Figure 5
Unfolding Trajectories of the Individual Talin Rod Subbundles
Once the talin rod is fragmented, the force will be transmitted via the terminal ends of the helices. Constant forces of 300 and 400 pN were thus applied to the termini of the fragments H1–H9 (A) and (D); H2–H8 (B) and (E); and H9–H12 (C) and (F) after 1 ns of equilibration. The distance between the terminal Cα-atoms of the fragments are plotted over time. The starting end-to-end distances of the terminal atoms of these helix bundles prior to stretching them were 3.6 nm (H1–H9), 7.9 nm (H2–H8), and 1.5 nm (H9–H12).
(A,D) Force applied to the H1–H9 fragment first leads to the unfolding of H9 (T1) and is then followed by the unfolding of H1 (T2). Further pulling with 400 pN results in the separation of bundles H2–H5 and H6–H8 from each other (T2–T3). Then, the C-terminal bundle H6–H8 is the first to be unraveled (T5). The 300 pN simulation does not lead to a separation of bundles within 2.7 ns (T3*) and shows similarity with T3 of the H2–H8 fragment (B) and (E).
(B,E) The 300 pN unfolding trajectory of the H2–H8 bundle not truncated along the “natural” interfaces shows sequential unfolding at the ends of the molecule (T1–T3). 400 pN force applied results in faster unfolding. The C-terminal part unfolds more easily indicating the lower stability of H6–H8 compared to H2–H5 (T7, T8).
(C,F) The H9–H12 fragment shows only negligible resistance against applied force even if pulled at 300 pN force.