期刊
CELL
卷 184, 期 18, 页码 4669-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2021.07.034
关键词
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资金
- National Institutes of Health (NIH) [P41-GM104601, R01-GM123455]
- Blue Waters at National Center for Supercomputing Applications (NCSA), Extreme Science and Engineering Discovery Environment (XSEDE) [MCA06N060]
- NIH grants from National Institute on Deafness and Other Communication Disorders [RO1 DC004274, DC012938]
- Jennifer and Bernard Lacroute Endowed Chair in Neuroscience
This study demonstrates how prestin in outer hair cells mediates signal amplification by coupling conformational changes to alterations in membrane surface area. Cryo-EM structures and computational studies reveal the allosteric coupling between the anion site and changes in the transmembrane domain and surrounding membrane. These findings provide insight into the electromotility of outer hair cells.
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.
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