Using 3D Modeling to Describe the Electromotility of the Outer Hair Cell Protein Prestin, and its Role in Sound Perception Among Mammals
Abstract
Prestin is a vital motor protein that enables auditory perception in mammals by modulating the shape of cochlear outer hair cells (OHCs) in response to environmental voltage. Part of the SLC26A5 anion transporter family, prestin excels at binding anions, which facilitates its oscillation through unique conformations. While salicylate has been demonstrated to induce reversible inhibition in prestin, the broader mechanisms of how this protein senses and transduces voltage into cellular movement are not fully understood. Crucial to sound amplification in the cochlea and the ability for OHCs to selectively respond to different sound frequencies is non-linear capacitance (NLC), wherein conformational changes are not linearly related to the voltage applied. Using 3D protein modeling with PyMOL, the inhibited state (7S9E) and sensor-up state (7S8X) of bottlenose dolphin (Tursiops truncatus) prestin were merged to create a new model. This model illustrates the flux in cross-sectional area within the transmembrane regions and emphasizes other key topological elements, such as the 14 gate and core transmembrane helices, the anion binding site, and the STAS domain. Helices TM3 and TM10, along with the active pocked formed by residues Gln97, Phe101, Phe137, Leu397, Ser398, and Arg399, play pivotal roles in ligand-bound dimer movement. Additional noncovalent forces such as pi stacking with Phe137 and hydrogen bonding with Ser398 enhance ligand binding stability. Notably, 13 amino acid replacements in echolocating mammals suggest convergent evolution among bats, whales, and dolphins. This structural exploration of prestin's electromotility thus aims to further unravel the intricate mechanisms of mammalian auditory perception.
Faculty Sponsors
Dr. Emily Schmitt Lavin, Dr. Arthur Sikora
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-3-2024 12:30 PM
End Date
4-4-2024 1:30 PM
Using 3D Modeling to Describe the Electromotility of the Outer Hair Cell Protein Prestin, and its Role in Sound Perception Among Mammals
Alvin Sherman Library
Prestin is a vital motor protein that enables auditory perception in mammals by modulating the shape of cochlear outer hair cells (OHCs) in response to environmental voltage. Part of the SLC26A5 anion transporter family, prestin excels at binding anions, which facilitates its oscillation through unique conformations. While salicylate has been demonstrated to induce reversible inhibition in prestin, the broader mechanisms of how this protein senses and transduces voltage into cellular movement are not fully understood. Crucial to sound amplification in the cochlea and the ability for OHCs to selectively respond to different sound frequencies is non-linear capacitance (NLC), wherein conformational changes are not linearly related to the voltage applied. Using 3D protein modeling with PyMOL, the inhibited state (7S9E) and sensor-up state (7S8X) of bottlenose dolphin (Tursiops truncatus) prestin were merged to create a new model. This model illustrates the flux in cross-sectional area within the transmembrane regions and emphasizes other key topological elements, such as the 14 gate and core transmembrane helices, the anion binding site, and the STAS domain. Helices TM3 and TM10, along with the active pocked formed by residues Gln97, Phe101, Phe137, Leu397, Ser398, and Arg399, play pivotal roles in ligand-bound dimer movement. Additional noncovalent forces such as pi stacking with Phe137 and hydrogen bonding with Ser398 enhance ligand binding stability. Notably, 13 amino acid replacements in echolocating mammals suggest convergent evolution among bats, whales, and dolphins. This structural exploration of prestin's electromotility thus aims to further unravel the intricate mechanisms of mammalian auditory perception.
