Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Structure. 2017 Apr 4;25(4):579-591.e4. doi: 10.1016/j.str.2017.02.002. Epub 2017 Mar 2.
Several unconventional myosins contain a highly charged single α helix (SAH) immediately following the calmodulin (CaM) binding IQ motifs, functioning to extend lever arms of these myosins. How such SAH is connected to the IQ motifs and whether the conformation of the IQ motifs-SAH segments are regulated by Ca fluctuations are not known. Here, we demonstrate by solving its crystal structure that the predicted SAH of myosin VIIa (Myo7a) forms a stable SAH. The structure of Myo7a IQ5-SAH segment in complex with apo-CaM reveals that the SAH sequence can extend the length of the Myo7a lever arm. Although Ca-CaM remains bound to IQ5-SAH, the Ca-induced CaM binding mode change softens the conformation of the IQ5-SAH junction, revealing a Ca-induced lever arm flexibility change for Myo7a. We further demonstrate that the last IQ motif of several other myosins also binds to both apo- and Ca-CaM, suggesting a common Ca-induced conformational regulation mechanism.
几种非传统肌球蛋白含有紧跟在钙调蛋白（CaM）结合 IQ 基序后的高度带电的单 α 螺旋（SAH），其作用是延长这些肌球蛋白的臂长。目前尚不清楚这种 SAH 与 IQ 基序的连接方式，以及 IQ 基序-SAH 片段的构象是否受 Ca 波动的调节。在这里，我们通过解决其晶体结构证明了肌球蛋白 VIIa（Myo7a）的预测 SAH 形成稳定的 SAH。Myo7a IQ5-SAH 片段与 apo-CaM 的复合物结构表明，SAH 序列可以延长 Myo7a 臂的长度。尽管 Ca-CaM 仍然与 IQ5-SAH 结合，但 Ca 诱导的 CaM 结合模式变化使 IQ5-SAH 连接的构象变软，为 Myo7a 揭示了 Ca 诱导的臂灵活性变化。我们进一步证明，其他几种肌球蛋白的最后一个 IQ 基序也与 apo-CaM 和 Ca-CaM 结合，这表明存在一种常见的 Ca 诱导构象调节机制。
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