Calmodulin Bound to the First IQ Motif Is Responsible for Calcium-dependent Regulation of Myosin 5a
Calmodulin Bound to the First IQ Motif Is Responsible for Calcium-dependent Regulation of Myosin 5a
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与第一个 IQ 基序结合的钙调蛋白负责肌球蛋白 5a 的钙依赖性调节
DOI：
10.1074/jbc.m112.343079
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发表时间：
2012-05-11
影响因子：
4.8
通讯作者：
Li, Xiang-dong
中科院分区：
文献类型：
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作者：
Lu, Zekuan;Shen, Mei;Li, Xiang-dong
肌球蛋白 5a 是迄今为止最典型的非常规肌球蛋白马达，参与沿肌动蛋白丝运输细胞器。众所周知，肌球蛋白 5a 通过其尾部以 Ca2+ 依赖性方式进行调节。肌球蛋白 5a 的肌动蛋白激活的 ATP 酶活性受到微摩尔浓度的 Ca2+ 刺激，并且钙调蛋白 (CaM) 与肌球蛋白 5a 重链的 IQ 基序结合，这一事实表明 Ca2+ 通过结合的 CaM 调节肌球蛋白 5a 的功能。然而，尚不清楚哪个 IQ 基序和结合的 CaM 负责 Ca2+ 依赖性调节以及 Ca2+ 如何影响头尾相互作用。在这里，我们发现第一个 IQ 基序 (IQ1) 中的 CaM 负责肌球蛋白 5a 的 Ca2+ 调节。此外，我们证明了 IQ1 中 CaM 的 C 叶片段对于介导肌球蛋白 5a 的 Ca2+ 调节是必需的，这表明 IQ1 中 CaM 的 C 叶片段参与了头部和尾部之间的相互作用。我们认为 Ca2+ 会诱导 IQ1 中 CaM C 叶的构象变化，并阻止头部和尾部之间的相互作用，从而激活运动功能。
Myosin 5a is as yet the best-characterized unconventional myosin motor involved in transport of organelles along actin filaments. It is well-established that myosin 5a is regulated by its tail in a Ca2+-dependent manner. The fact that the actin-activated ATPase activity of myosin 5a is stimulated by micromolar concentrations of Ca2+ and that calmodulin (CaM) binds to IQ motifs of the myosin 5a heavy chain indicates that Ca2+ regulates myosin 5a function via bound CaM. However, it is not known which IQ motif and bound CaM are responsible for the Ca2+-dependent regulation and how the head-tail interaction is affected by Ca2+. Here, we found that the CaM in the first IQ motif (IQ1) is responsible for Ca2+ regulation of myosin 5a. In addition, we demonstrate that the C-lobe fragment of CaM in IQ1 is necessary for mediating Ca2+ regulation of myosin 5a, suggesting that the C-lobe fragment of CaM in IQ1 participates in the interaction between the head and the tail. We propose that Ca2+ induces a conformational change of the C-lobe of CaM in IQ1 and prevents interaction between the head and the tail, thus activating motor function.