Fig. 4
An optimized model of the sequestered state of β-cardiac myosin. a β-cardiac myosin sequestered state modeled from the cardiac myosin S1 PPS structure. This model results from optimization of the intra-head interactions that occur upon formation of the IHM59 with two asymmetric heads: the free head (FH) and the blocked head (BH). b Detailed analysis of a region of the interface involving the FH-converter and the BH-U50 subdomain. Note that the top loop plays a major role. c Surface of the FH-mesa and the FH-converter involved in interactions with the BH. d Surface of the BH-mesa and the BH-converter involved in interactions with the FH. A putative surface of interaction with the partner MyBP-C is also represented. The regions of the interface that are part of the mesa are labeled with a * and a # on the FH and on the BH, respectively. e Schematic representation analyzing the prerequisites to form the IHM. On top, different myosin conformations illustrate the differences in position of the lever arm in the PR and the PPS states. Two heads in the PPS conformation are shown in the sequestered state. On the center, a schematic representation of the two states adopted by the heavy meromyosin (HMM) is shown. On the bottom, the different conformations of the top loop present in the PR crystal structure and in the BH and the FH of the sequestered state are displayed in cartoon representation. To form the sequestered state, the lever arms of the FH and BH heads must adopt conformations, in particular for the top loop. Note, however, that the pliant region remains close to the conformation of the WT PPS structure. Dynamics at the ELC/converter interface of the two heads of the myosin dimer is thus important to promote sequestration of the heads
