TY - JOUR T1 - Cryo-EM Structures of Prestin and the Molecular Basis of Outer Hair Cell Electromotility JF - bioRxiv DO - 10.1101/2021.08.06.455374 SP - 2021.08.06.455374 AU - Navid Bavi AU - Michael David Clark AU - Gustavo F. Contreras AU - Rong Shen AU - Bharat Reddy AU - Wieslawa Milewski AU - Eduardo Perozo Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/08/08/2021.08.06.455374.abstract N2 - The voltage-dependent motor protein, Prestin (SLC26A5) is responsible for the electromotive behavior of outer hair cells (OHCs). Here, we determined the structure of dolphin Prestin in six distinct states using single particle cryo-electron microscopy. Structural and functional data suggest that Prestin adopts a unique and complex set of states, tunable by the identity of bound anions. Complexes with the inhibitor salicylate show that it competes for the anion-binding site of Prestin. These conformations reveal a novel mechanism of area expansion that depends on the helix flexibility and conformational transitions at the membrane protein interface and putatively affects the physical state of the surrounding membrane. These observations illuminate the structural basis of Prestin electromotility, a key component of the mammalian cochlear amplifier.Competing Interest StatementThe authors have declared no competing interest. ER -