Hearing involves two fundamental processes: mechano-electrical transduction and signal amplification. Despite decades of studies, the molecular bases for both remain elusive. Here, we show how prestin, the electromotive molecule of outer hair cells (OHCs) that senses both voltage and membrane tension, mediates signal amplification by coupling conformational changes to alterations in membrane surface area. Cryoelectron microscopy (cryo-EM) structures of human prestin bound with chloride or salicylate at a common “anion site” adopt contracted or expanded states, respectively. Prestin is ensconced within a perimeter of well-ordered lipids, through which it induces dramatic deformation in the membrane and couples protein conformational changes to the bulk membrane. Together with computational studies, we illustrate how the anion site is allosterically coupled to changes in the transmembrane domain cross-sectional area and the surrounding membrane. These studies provide insight into OHC electromotility by providing a structure-based mechanism of the membrane motor prestin.

听觉涉及两个基本过程：机电传导和信号放大。尽管经过数十年的研究，两者的分子基础仍然难以捉摸。在这里，我们展示了 prestin（外毛细胞 (OHC) 的电动分子，可感知电压和膜张力）如何通过将构象变化与膜表面积的变化耦合来介导信号放大。人 prestin 与氯化物或水杨酸盐在共同“阴离子位点”结合的冷冻电子显微镜 (cryo-EM) 结构分别采用收缩或膨胀状态。 Prestin 隐藏在有序脂质的周边内，通过它引起膜的剧烈变形，并将蛋白质构象变化与本体膜结合起来。结合计算研究，我们说明了阴离子位点如何与跨膜域横截面积和周围膜的变化变构耦合。这些研究通过提供基于结构的膜电机 prestin 机制，提供了对 OHC 电动性的深入了解。