Myosin III-mediated cross-linking and stimulation of actin bundling activity of Espin
Myosin III-mediated cross-linking and stimulation of actin bundling activity of Espin
复制标题
肌球蛋白 III 介导的交联和刺激 Espin 的肌动蛋白成束活性。
DOI：
10.7554/elife.12856
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发表时间：
2016-01-19
期刊：
影响因子：
7.7
通讯作者：
Zhang, Mingjie
中科院分区：
文献类型：
--
作者：
Liu, Haiyang;Li, Jianchao;Zhang, Mingjie
III类肌球蛋白（Myo3）和肌动蛋白捆绑蛋白Espin在调节脊椎动物毛细胞中静纤毛的发育和维持中起关键作用，并且它们的缺陷导致遗传性听力障碍。Myo3通过其尾部同源性I基序（THDI）与Espin1相互作用，然而Myo3如何特异性地通过Espin1调节肌动蛋白束的组装和稳定尚不清楚。在这里，我们发现，Myo3 THDI包含一对重复序列能够独立和强烈结合的锚蛋白重复的Espin1，揭示了一个意想不到的Myo3介导的Espin1的交联机制。Myo3与Espin1复合物的结构不仅阐明了结合机制，而且揭示了Myo3诱导Espin1自抑制机制的释放。我们还提供了证据表明，Myo3介导的交联可以进一步促进肌动蛋白纤维成束活性的Espin1。
Class III myosins (Myo3) and actin-bundling protein Espin play critical roles in regulating the development and maintenance of stereocilia in vertebrate hair cells, and their defects cause hereditary hearing impairments. Myo3 interacts with Espin1 through its tail homology I motif (THDI), however it is not clear how Myo3 specifically acts through Espin1 to regulate the actin bundle assembly and stabilization. Here we discover that Myo3 THDI contains a pair of repeat sequences capable of independently and strongly binding to the ankyrin repeats of Espin1, revealing an unexpected Myo3-mediated cross-linking mechanism of Espin1. The structures of Myo3 in complex with Espin1 not only elucidate the mechanism of the binding, but also reveal a Myo3-induced release of Espin1 auto-inhibition mechanism. We also provide evidence that Myo3-mediated cross-linking can further promote actin fiber bundling activity of Espin1.