Allosteric Communication in Myosin V: From Small Conformational Changes to Large Directed Movements
Figure 10
Structural rearrangement of the myosin subdomains along the rigor-like/post-rigor NMSM path; see also the corresponding sections in the text.
The energy-minimized rigor-like structure is shown in colors; the NMSM post-rigor conformation is in grey with the nucleotide-binding elements shown in pale colors. The color code for the motor subdomains is the same as in Figure 2. The red arrows indicate the direction of motion of the subdomains along the NMSM transition. Insets on the left-hand side of each panel help to localize the structural elements which are being discussed. (A) N/U50 subdomains. Large-amplitude rotation of the N and U50 subdomains coupled to a local rearrangement in the ATP binding site; the screw axes û and nˆ are shown. (B) Structural transition of the nucleotide-binding elements. The two perpendicular views show the way switch I approaches the P-loop and moves “over” it. In doing so, the distance between Ser 218 and Thr 170, and Glu 204 and Lys 174 is substantially reduced (top), as reported in Table 4. In the ATP-bound state, the former pair of residues contributes to the coordination of the Mg2+ ion, while the latter pair makes a salt-bridging interaction. (C) N/C subdomains. On top is shown the network of H-bonds at the N/C interface responsible for the coupling. On bottom is shown the large-amplitude rotation of the N subdomain promoting the repositioning of the converter. The movement of the N-terminal is transmitted to the converter by specific interactions (shown as cyan dashed solid lines) involving Loop 76–81 (in violet). (D) L50/C subdomains. On the left are shown the large-amplitude motions of the converter and the L50 subdomain, which contribute to the opening of the U50/L50 cleft; on the right are shown the specific interactions involving the relay helix responsible for the L50/C coupling (on top) and the effect of the motion of L50 on the position of switch II (on bottom). The large-amplitude rotation of the L50 subdomain, which completes the opening of the U50/L50 cleft, is coupled to a rigid-body movement of switch II that breaks the rigor-like H-bonding interaction (Phe 441 - Ala 684) with the SH1 helix (see Table 4). (E) Reorientation of the lever arm. The lever arm, the relay helix, and the SH1 helix are shown in yellow, red, and magenta, respectively. Along with the orthogonal view (see panel C, on bottom), the picture shows how the displacement of the N subdomain is transmitted to the converter and transformed into a torque about axis ĉ that reorients the lever arm. The analysis suggests that the “short swinging” of the lever arm as observed in the X-ray structures [36] is a consequence of the rigor-like/post-rigor displacement of the converter.