Cryo-EM structures reveal specialization at the myosin VI-actin interface and a mechanism of force sensitivity

• Main Authors: Pinar S Gurel, Laura Y Kim, Paul V Ruijgrok, Tosan Omabegho, Zev Bryant, Gregory M Alushin
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2017-12-01
• Series: eLife
• Subjects: molecular motors; cytoskeleton; myosin; actin; Cryo-EM
• Online Access: https://elifesciences.org/articles/31125

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.