7s9a

Cryo-EM Structure of dolphin Prestin: Inhibited I (Chloride + Salicylate)

spinqualitylabelsall models 7s9a, resolution 3.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.8Å Ligands: SAL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The voltage-dependent motor protein Prestin (SLC26A5) is responsible for the electromotive behavior of outer hair cells and underlies the cochlear amplifier(1). Knock out or impairment of Prestin causes severe hearing loss(2-5). Despite Prestin's key role 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 SO4(2-)). 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 novel conformation. Our data suggests that the bound anion together with its coordinating charged residues and helical dipole act as a dynamic voltage sensor. Analysis of all anion-dependent conformations reveals how structural rearrangements in the voltage sensor are coupled to conformational transitions at the protein-membrane interface, suggesting a novel mechanism of area expansion. Visualization of Prestin's electromotility cycle distinguishes Prestin from closely related SLC26 anion transporters, highlighting the basis for evolutionary specialization of the mammalian cochlear amplifier at high resolution. Prestin's conformational cycle underlies outer hair cell electromotility.,Bavi N, Clark MD, Contreras GF, Shen R, Reddy BG, Milewski W, Perozo E Nature. 2021 Oct 25. pii: 10.1038/s41586-021-04152-4. doi:, 10.1038/s41586-021-04152-4. PMID:34695838 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Prestin

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