Fig. 6: Effects of Mava and OM on the β-cardiac myosin sequestered state.

a Superimposition of the cryo-EM β-cardiac IHM structure (cartoon, PDB code 8ACT¹¹ on the S1 structure of β-cardiac myosin complexed to OM (PDB 5N69²⁹), Superimposition on the motor domain of the blocked head (BH) (residues 1–707). The presence of OM induces several differences in the Transducer and in the Converter (indicated in dashed lines). b Superimposition of the β-cardiac IHM structure on the two molecules of the asymmetric unit of PPS-S1-Mava (ribbon, in black) superimposed on the head-head interface (residues 329–447 of the BH and residues 498–518, 708–780 on the FH, RMSD 0.5 Å on 112 Cα). c Superimposition of a molecule of the asymmetric unit of PPS-S1-Mava on the BH (residue 1–707) of the β-cardiac myosin IHM. d Zoom at the head-head interface of the superimposition of PPS-S1-OM and the FH of the sequestered state. The FH is represented as a transparent surface to highlight the surface of interaction. The differences between PPS-S1-OM and the FH making the presence of OM incompatible with the IHM are indicated in red dashed lines. These differences also disrupt the electrostatic interaction between R169 and E717 (indicated with a red star) that is present in the head-head interface of the IHM. e Zoom at the head-head interface of the superimposition of PPS-S1-Mava and the FH of the sequestered state. The structures are highly similar and the presence of Mava does not disrupt the interaction between R169 and E717. The binding of Mava is thus compatible with the IHM.