Visualization of head-head interactions in the inhibited state of smooth muscle myosin

The structural basis for the phosphorylation-dependent regulation of smooth muscle myosin ATPase activity was investigated by forming two-dimensional (2-D) crystalline arrays of expressed un phosphorylated and thiophosphoryla ted smooth muscle heavy meromyosin (HMM) on positively charged lipid monola yers. A comparison of averaged 2-D projections of both forms at 2.3-nm reso lution reveals distinct structural differences, In the active, thiophosphor ylated form, the two heads of HMM interact intermolecularly with adjacent m olecules. In the unphosphorylated or inhibited state, intramolecular intera ctions position the actin-binding interface of one head onto the converter domain of the second head, thus providing a mechanism whereby the activity of both heads could be inhibited.