PT  - JOURNAL ARTICLE
AU  - Bavi, Navid
AU  - Clark, Michael David
AU  - Contreras, Gustavo F.
AU  - Shen, Rong
AU  - Reddy, Bharat
AU  - Milewski, Wieslawa
AU  - Perozo, Eduardo
TI  - Cryo-EM Structures of Prestin and the Molecular Basis of Outer Hair Cell Electromotility
AID  - 10.1101/2021.08.06.455374
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.06.455374
4099  - http://biorxiv.org/content/early/2021/08/08/2021.08.06.455374.short
4100  - http://biorxiv.org/content/early/2021/08/08/2021.08.06.455374.full
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.