Conformational changes in the myosin motor domain produce force on actin. Structural organization of the myosin motor. (A) Ribbon diagram of the myosin S1 motor domain displayed in two orientations. The secondary structure of the molecule is colored according to the subdomains of the protein, including the upper 50 kD domain (U50, dark purple), the lower 50 kD domain (L50, light purple), the N-terminal domain (blue), converter (cyan), lever arm (magenta), and the transducer region (light blue). The nucleotide-binding site is marked by a space-filling model of ADP/Mg. This figure was adapted from Doran and Lehman (2021) and uses the coordinates deposited in PDB ID 5H53. (B) Schematic of the myosin force generating mechanism. β-cardiac myosin II undergoes conformational changes that are paired to actin binding and nucleotide-hydrolysis product release steps in order to generate the requisite force that results in cardiac muscle contraction. This figure describes each step of the cycle and the rearrangements of the myosin head, including cleft closure and the movement of the lever arm during the powerstroke. Each subdomain of the molecule is colored as in A, while the force generating steps are shaded red. In order to provide clarity, the phosphate release step, which occurs after hydrolysis and before the first step of the powerstroke, was not included in this figure. The step we focus on in this paper, ADP-release, is outlined in the dashed box.