Practice question

Mechanistic model of myosin step size explains velocity differences among isoforms. Lever arm hypothesis states small conformational change of converter domain upon phosphate release rotation about 10 degrees amplified by rigid lever arm helical neck decorated with IQ motifs bound to light chains acting as fulcrum. Step size roughly equals lever length times angular change, so each IQ motif about 5 to 6 nanometer contributes. Constructing chimeras fusing artificial alpha actinin repeats or duplicating IQ motifs increased sliding speed linearly in motility assays without altering ATPase kcat, confirming length determines speed. Myosin V with six IQ motifs long lever moves 36 nanometer step fast cargo transport, myosin II with two IQ short lever 5 to 10 nanometer slower but ensemble force generation. Regulatory light chain phosphorylation changes recruitment and duty ratio in smooth muscle, actin length affects number of interacting heads not intrinsic speed, ATP concentration alters velocity only below Km about 50 micromolar. Therefore intrinsic determinant of maximal speed at saturating ATP is length of lever arm translating small catalytic domain rotation into amplified translation and faster sliding.