RT Journal Article
SR Electronic
T1 Cryo-EM Structures of Prestin and the Molecular Basis of Outer Hair Cell Electromotility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.06.455374
DO 10.1101/2021.08.06.455374
A1 Bavi, Navid
A1 Clark, Michael David
A1 Contreras, Gustavo F.
A1 Shen, Rong
A1 Reddy, Bharat
A1 Milewski, Wieslawa
A1 Perozo, Eduardo
YR 2021
UL http://biorxiv.org/content/early/2021/08/08/2021.08.06.455374.abstract
AB 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.