# Structural basis of Outer Hair Cell Electromotility at High Resolution

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2021 · $506,157

## Abstract

Project Summary
The overall, long-term goal of this project is to understand the molecular mechanism of that define the cochlear
amplifier in outer hair Cells (OHC). Specifically, we will focus on the voltage-driven motor Prestin, a unique
member of the SCL26 family of transporters found in the basolateral membranes of OHCs. Although Prestin
has been studied extensively though functional approaches, the basic mechanistic understanding of this
fundamental component of the cochlear amplifier remain to be solved. In spite of the richness of the existing
functional data, the lack of a high resolution structure is a key missing element in defining its mechanism at a
molecular level. This is particularly so for the two fundamental aspects of Prestin’s mechanism of action: the
process underlying voltage sensing and the molecular mechanism of electromotility. In light of exciting new
preliminary data at the core of this proposal we will be able to study the functional behavior, high resolution
structure and dynamics of Prestin as a biological piezoelectric device. To do so, we plan to experimentally
address several fundamental questions: What is the physical basis of the energy transduction steps, starting
with transmembrane voltage changes and culminating in protein (and ultimately OHC) motion? What are the
structures of the key functional states in its native, bilayer-embedded form? Where in the molecule does
mechanical transduction occur? And how? What are the physical basis of the Prestin-bilayer interaction?
Functional studies will be designed to understand the physical basis of energy transduction. Information on the
high resolution structure of functionally relevant conformations, conformational dynamics and energetic
relationship of Prestin with its surrounding lipid bilayer will be obtained from cryo-EM, electrophysiology and
Fluorescence microscopy experiments. The data will be interpreted to generate high resolution structures of
the different stages of the electromechanical transduction. We suggest that the advent of new cryo-EM
approaches to the analysis of structure and dynamics in membrane proteins in their native lipidic environment
shall open an exciting new experimental avenue. This information will impact our understanding of
physiologically important events such as hearing, high frequency amplification and signal transduction.

## Key facts

- **NIH application ID:** 10317974
- **Project number:** 1R01DC019833-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Eduardo A Perozo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $506,157
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317974

## Citation

> US National Institutes of Health, RePORTER application 10317974, Structural basis of Outer Hair Cell Electromotility at High Resolution (1R01DC019833-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10317974. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*