Sotomayor Marcos, Corey David P, Schulten Klaus
Department of Physics, University of Illinois at Urbana-Champaign and Beckman Institute for Advanced Science and Technology, Urbana, Illinois 61801, USA.
Structure. 2005 Apr;13(4):669-82. doi: 10.1016/j.str.2005.03.001.
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.
脊椎动物毛细胞中的机械转导涉及一个在生物物理上定义的弹性元件（“门控弹簧”），该元件牵拉转导通道。纤毛顶部连接丝是由钙黏蛋白23构成的细丝，连接毛细胞束中相邻的静纤毛，有人认为它就是门控弹簧。然而，在果蝇、斑马鱼和小鼠中介导机械转导的瞬时受体电位（TRP）通道，其胞质结构域通常含有大量锚蛋白重复序列，这些序列也是门控弹簧的候选者。我们利用含有一个钙黏蛋白重复序列或4个及12个锚蛋白重复序列的蛋白质晶体结构，以及17个和24个锚蛋白重复序列的模型，通过分子动力学模拟研究了钙黏蛋白和锚蛋白重复序列的弹性特性。我们发现，大型锚蛋白重复结构的伸展性和刚度与门控弹簧模型预测的结果相符。我们的研究结果表明，TRPA1和TRPN1通道的锚蛋白重复序列充当了机械转导的门控弹簧。
