Figure 3.

Docking of unphosphorylated HMM onto actin. (A) The “free” head of the HMM model is oriented on actin by using the actin-binding domain of rigor skeletal muscle actomyosin (Inset) as the reference. The smooth muscle S1 with a transition state analog at the active site appears with the lever arm up (15) in contrast to the lever arm down-postpowerstroke conformation of skeletal muscle actomyosin (35). The HMM model, when oriented via the actin-binding domain, verifies that one head can interact with actin without steric hindrance from the second head. The orientation of the double-headed myosin in B represents the arrangement with the S2_lll segment oriented toward the direction of force transmission, as would occur within the muscle lattice. The head orientations in this configuration do not favor actin binding by either head.