Figure 6. Examples of specific P-loop interactions that appear to modulate stability of specific P-loop states.

(A) MYO6, a high duty ratio motor, features an interaction between the backbone carbonyl oxygen of S153 (analogous to S180 in MYH7) and the side chain amide group of K670 on the switch-II loop. Myosin-IIs (MYH13, MYH7, and MYH10) feature an isoleucine at this position, eliminating this A state-stabilizing interaction. (B) In MYO6, the sidechain of K670 interacts tightly with the S153 backbone, whereas in MYH7, there is virtually no direct interaction between the homologous positions (S180 and I674). This presumably leads to a stabilization of state A in MYO6, contributing to its preference for the A state over the B state. An approximate cutoff distance for interaction, 3 Å, is marked as a vertical line. (C) In MYH7, a low duty ratio motor with a high relative B state probability permits interaction between the backbone carbonyl oxygen of S242 and the sidechain hydroxyl group of S180. This geometry is permitted by a small alanine sidechain at position 463. (D) When the P-loop is in state B, the sidechain hydroxyl group of S180 hydrogen bonds with the backbone carbonyl oxygen of S242 in MYH7, whereas MYO7A’s homologous positions do not interact in either state. This interaction presumably increases the relative probability of the B state relative to the A state and could in part account for MYH7’s higher propensity to adopt this excited conformation. The reference distance 3 Å is marked as a vertical line.