Single particle cryo-EM structure of the outer hair cell motor protein prestin

• Published in: Nature communications Vol. 13; no. 1; p. 290
• Main Authors: Butan, Carmen, Song, Qiang, Bai, Jun-Ping, Tan, Winston J. T., Navaratnam, Dhasakumar, Santos-Sacchi, Joseph
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12-01-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 13; 13/106; 13/109; 631/378/2619/1533; 631/45/612/1237; 631/535/1258/1259; 9/74; Animals; Anion Transport Proteins; Anions; Binding Sites; Capacitance; CHO Cells; Cochlea; Cricetulus; Cryoelectron Microscopy; Dimers; Domains; Electric potential; Electron microscopy; Gerbillinae; Hair; Hair Cells, Auditory, Outer - metabolism; Hair Cells, Vestibular - metabolism; Humanities and Social Sciences; Ion Transport; Membrane Proteins - chemistry; Molecular Motor Proteins - chemistry; Molecular Motor Proteins - metabolism; Molecular motors; multidisciplinary; Mutation; Piezoelectricity; Protein Domains; Proteins; Salicylic acid; Science; Science (multidisciplinary); Sigma factor; Structural analysis; Sulfate transporter; Sulfate Transporters - chemistry; Transmembrane domains; Voltage
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27915-z

The mammalian outer hair cell (OHC) protein prestin (Slc26a5) differs from other Slc26 family members due to its unique piezoelectric-like property that drives OHC electromotility, the putative mechanism for cochlear amplification. Here, we use cryo-electron microscopy to determine prestin’s structure at 3.6 Å resolution. Prestin is structurally similar to the anion transporter Slc26a9. It is captured in an inward-open state which may reflect prestin’s contracted state. Two well-separated transmembrane (TM) domains and two cytoplasmic sulfate transporter and anti-sigma factor antagonist (STAS) domains form a swapped dimer. The transmembrane domains consist of 14 transmembrane segments organized in two 7+7 inverted repeats, an architecture first observed in the bacterial symporter UraA. Mutation of prestin’s chloride binding site removes salicylate competition with anions while retaining the prestin characteristic displacement currents (Nonlinear Capacitance), undermining the extrinsic voltage sensor hypothesis for prestin function.
Prestin, expressed in outer hair cell (OHC), belongs to the Slc26 transporter family and functions as a voltage-driven motor that drives OHC electromotility. Here, the authors report cryo-EM structure and characterization of gerbil prestin, with insights into its mechanism of action.