7S9C

Cryo-EM Structure of dolphin Prestin: Sensor Down II (Expanded II) state

Summary for 7S9C

• Entry DOI: 10.2210/pdb7s9c/pdb
• EMDB information: 24932
• Descriptor: Prestin (1 entity in total)
• Functional Keywords: outer hair cells, electromotility, mechanotransduction, hearing, deafness, frequency sensation, echolocation, slc26, slc26a5, motor protein
• Biological source: Tursiops truncatus (Atlantic bottle-nosed dolphin, Delphinus truncatus)
• Total number of polymer chains: 2
• Total formula weight: 161947.50

Authors

Bavi, N.,Clark, M.D.,Contreras, G.F.,Shen, R.,Reddy, B.G.,Milewski, W.,Perozo, E. (deposition date: 2021-09-20, release date: 2021-11-03, Last modification date: 2024-06-05)

Primary citation

Bavi, N.,Clark, M.D.,Contreras, G.F.,Shen, R.,Reddy, B.G.,Milewski, W.,Perozo, E.
The conformational cycle of prestin underlies outer-hair cell electromotility.
Nature, 600:553-558, 2021

PubMed Abstract: The voltage-dependent motor protein prestin (also known as SLC26A5) is responsible for the electromotive behaviour of outer-hair cells and underlies the cochlear amplifier. Knockout or impairment of prestin causes severe hearing loss. Despite the key role of prestin in hearing, the mechanism by which mammalian prestin senses voltage and transduces it into cellular-scale movements (electromotility) is poorly understood. Here we determined the structure of dolphin prestin in six distinct states using single-particle cryo-electron microscopy. Our structural and functional data suggest that prestin adopts a unique and complex set of states, tunable by the identity of bound anions (Cl or SO). Salicylate, a drug that can cause reversible hearing loss, competes for the anion-binding site of prestin, and inhibits its function by immobilizing prestin in a new conformation. Our data suggest that the bound anion together with its coordinating charged residues and helical dipole act as a dynamic voltage sensor. An analysis of all of the anion-dependent conformations reveals how structural rearrangements in the voltage sensor are coupled to conformational transitions at the protein-membrane interface, suggesting a previously undescribed mechanism of area expansion. Visualization of the electromotility cycle of prestin distinguishes the protein from the closely related SLC26 anion transporters, highlighting the basis for evolutionary specialization of the mammalian cochlear amplifier at a high resolution.

PubMed: 34695838
DOI: 10.1038/s41586-021-04152-4

Experimental method

ELECTRON MICROSCOPY (6.7 Å)