Cryo-EM structures reveal specialization at the myosin VI-actin interface and a mechanism of force sensitivity
- National Heart, Blood, and Lung Institute, United States
- Stanford University, United States
Abstract
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.
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Funding
W. M. Keck Foundation
- Zev Bryant
Human Frontier Science Program (Long-Term Fellowship)
- Paul V Ruijgrok
National Heart, Lung, and Blood Institute
- Gregory M Alushin
Rockefeller University (Women & Science Fellowship)
- Pinar S Gurel
National Institutes of Health (F32GM094420)
- Tosan Omabegho
National Institutes of Health (1DP2 OD004690)
- Zev Bryant
National Institutes of Health (5DP5OD017885)
- Gregory M Alushin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Gurel et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cryo-EM structures reveal specialization at the myosin VI-actin interface and a mechanism of force sensitivity
eLife 6:e31125.
https://doi.org/10.7554/eLife.31125
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