素的形状周期是外毛细胞电流性的基础
Navid Bavi1, Michael David Clark1, Gustavo F Contreras1
1Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA.
Nature
|October 25, 2021
概括
电压依赖的运动蛋白质普雷斯对于听觉至关重要, 通过结合的离子和形状变化感知电压. 这项研究揭示了它的详细结构和电动机制,
科学领域:
- 结构生物学
- 分子生物物理学
- 听觉神经科学
背景情况:
- 普雷斯 (SLC26A5) 是一种电压依赖的运动蛋白,对外皮细胞功能和耳放大器至关重要,对哺乳动物听力至关重要.
- 导致严重的听力损失, 这强调了它的重要性.
- 普雷斯感知电压并产生运动 (电动性) 的确切机制尚不清楚.
研究的目的:
- 在各种功能状态下阐明哺乳动物的高分辨率结构.
- 了解普雷斯如何感知电压并将其转化为机械运动.
- 研究阴离子和酸盐等药物的作用.
主要方法:
- 使用单颗粒冷电子显微镜 (cryo-EM) 来确定海豚的结构.
- 已经确定了六种不同的形状.
- 进行了功能性测试,以评估离子结合和酸盐对普雷斯电流性的影响.
主要成果:
- 这项研究确定了海豚在六个不同的状态中的结构,揭示了复杂的形状.
- 通过结合的离子 (Cl-或SO42-) 调节Prestin的结构状态,这些离子与带电残留物和螺旋双极相互作用,形成动态电压传感器.
- 酸盐是一种普雷斯的抑制剂,它与位结合,使蛋白质停滞不前,从而破坏其功能.
- 提出了一个新的区域扩张机制,涉及电压传感器和蛋白质膜接口的合重新安排.
结论:
- 结合的离子及其相关的蛋白质元素作为精密的电压传感器.
- 结构重组揭示了普雷斯的区域扩张和电动性.
- 这些发现区分了普雷斯与其他SLC26传送器,并解释了耳放大器的进化专业化.
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