Cryo-EM structures of the myosin VI motor domain bound to F-actin reveal unique actin-myosin interface interactions and structural rearrangements that explain force sensitivity.
High-resolution cryo-EM structures of the myosin VI-actin interface reveal evolutionary specialization and a structural mechanism for force sensitivity during the mechanochemical cycle.
Despite extensive scrutiny of the myosin superfamily, the lack of high-resolution structures of actin-bound states has prevented a complete description of its mechanochemical cycle and limited insight into how sequence and structural diversification of the motor domain gives rise to specialized functional properties. Here we present cryo-EM structures of the unique minus-end directed myosin VI motor domain in rigor (4.6 Å) and Mg-ADP (5.5 Å) states bound to F-actin. Comparison to the myosin IIC-F-actin rigor complex reveals an almost complete lack of conservation of residues at the actin-myosin interface despite preservation of the primary sequence regions composing it, suggesting an evolutionary path for motor specialization. Additionally, analysis of the transition from ADP to rigor provides a structural rationale for force sensitivity in this step of the mechanochemical cycle. Finally, we observe reciprocal rearrangements in actin and myosin accompanying the transition between these states, supporting a role for actin structural plasticity during force generation by myosin VI.
Gurel et al. (Mon,) reported a other. Cryo-EM structural analysis was evaluated on Protein structure resolution of myosin VI bound to F-actin. Cryo-EM structures of the myosin VI motor domain bound to F-actin reveal unique actin-myosin interface interactions and structural rearrangements that explain force sensitivity.