Key result
A myosin VI/V chimera lacking the lever arm extension generated the same stepping patterns as wild-type myosin VI, indicating the extension is not required for the adjacent binding state.
The lever arm extension of myosin VI is not necessary for its unique adjacent binding state, supporting the parallel lever arms model for its stepping mechanism.
No immediate clinical implications for cardiac contractility; extends parallel lever arms model but leaves translation to human myosins open.
Myosin VI is a processive myosin that has a unique stepping motion, which includes three kinds of steps: a large forward step, a small forward step and a backward step. Recently, we proposed the parallel lever arms model to explain the adjacent binding state, which is necessary for the unique motion. In this model, both lever arms are directed the same direction. However, experimental evidence has not refuted the possibility that the adjacent binding state emerges from myosin VI folding its lever arm extension (LAE). To clarify this issue, we constructed a myosin VI/V chimera that replaces the myosin VI LAE with the IQ3-6 domains of the myosin V lever arm, which cannot fold, and performed single molecule imaging. Our chimera showed the same stepping patterns as myosin VI, indicating the LAE is not responsible for the adjacent binding state.
No takes yet. Share an insight, caveat, or question.
Ikezaki et al. (2015) studied this question. Myosin VI/V chimera vs. Wild-type Myosin VI was evaluated on Stepping patterns (large, small, and backward steps). A myosin VI/V chimera lacking the lever arm extension generated the same stepping patterns as wild-type myosin VI, indicating the extension is not required for the adjacent binding state.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: