In search of the hair-cell gating spring: Elastic properties of ankyrin and cadherin repeats
In search of the hair-cell gating spring: Elastic properties of ankyrin and cadherin repeats
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DOI：
10.1016/j.str.2005.03.001
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发表时间：
2005-04-01
期刊：
影响因子：
5.7
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Sotomayor, M;Corey, DP;Schulten, K
脊椎动物毛细胞的机械转导涉及生物物理定义的弹性元件（“门控弹簧”），它拉动转导通道。在毛细胞束中，由钙粘蛋白23组成的细丝连接相邻的立体纤毛，被认为是门弹簧。然而，在果蝇、斑马鱼和小鼠中介导机械转导的TRP通道通常具有含有大量锚蛋白重复序列的细胞质结构域，这些结构域也是门控弹簧的候选者。我们通过分子动力学模拟，探索了钙粘蛋白和锚蛋白重复序列的弹性特性，使用了具有1个钙粘蛋白重复序列或4个和12个锚蛋白重复序列的蛋白质晶体结构，并使用了17个和24个锚蛋白重复序列的模型。大型锚固重复结构的拉伸和刚度与闸门-弹簧模型的预测结果吻合。我们的研究结果表明，TRPA1和TRPN1通道的锚蛋白重复是机械转导的门控弹簧。
Mechanotransduction in vertebrate hair cells involves a biophysically defined elastic element (the "gating spring") that pulls on the transduction channels. The tip link, a fine filament made of cadherin 23 linking adjacent stereocilia in hair-cell bundles, has been suggested to be the gating spring. However, TRP channels that mediate mechanotransduction in Drosophila, zebrafish, and mice often have cytoplasmic domains containing a large number of ankyrin repeats that are also candidates for the gating spring. We have explored the elastic properties of cadherin and ankyrin repeats through molecular dynamics simulations using crystallographic structures of proteins with one cadherin repeat or 4 and 12 ankyrin repeats, and using models of 17 and 24 ankyrin repeats. The extension and stiffness of large ankyrin-repeat structures were found to match those predicted by the gating-spring model. Our results suggest that ankyrin repeats of TRPA1 and TRPN1 channels serve as the gating spring for mechanotransduction.