Structural Mechanism of Prestin-Membrane Mechanotransduction.

Area of Science:

• Biophysics
• Molecular Biology
• Auditory Neuroscience

Background:

• Sound frequency discrimination relies on prestin (SLC26A5), the piezoelectric motor in outer hair cells.
• The precise mechanism of prestin's electrically driven conformational changes and its dependence on membrane mechanics is not fully understood.

Purpose of the Study:

• To elucidate the role of membrane forces in prestin's conformational transitions.
• To understand how prestin mediates electro-mechanical transduction for auditory function.

Main Methods:

• Single particle cryo-electron microscopy (cryo-EM) of nanodiscreconstituted prestin.
• Mutagenesis studies, H/D exchange mass spectrometry, and NLC measurements.
• Analysis of prestin structures under varying lipid composition and membrane thickness.

Main Results:

• Membrane forces strongly influence prestin's conformational states, complementing transmembrane voltage effects.
• Membrane thinning induces a shift in prestin from compact to expanded conformations, mimicking outer hair cell electromotility.
• Zebrafish SLC26A5 transporters exhibit distinct elevator movements, differing from mammalian prestin.

Conclusions:

• Prestin's conformational changes are modulated by membrane tension, revealing reciprocal electro-mechanical transduction.
• This mechanism is essential for translating membrane tension into motor movement during sound-evoked vibrations.
• High-resolution structural insights advance our understanding of cochlear amplification and hearing.