Meeting Abstract
Prestin is the 5th member of an eleven-member membrane transporter superfamily of SLC26A proteins. Prestin primarily functions as a motor protein with unique capability of performing direct and reciprocal electromechanical conversion on microsecond time scale. Prestin-based outer hair cell motility is responsible for the exquisite sensitivity and frequency selectivity seen in the mammalian cochlea. Although prestin is also expressed in the zebrafish, amphibian, and reptilian hair cells, it functions as an ion transporter. During evolution, the ion transport capability, typical of SLC26A members, was replaced by an innovation that is unique to the therian OHCs with a voltage dependent motility. In this presentation, we will review recent work from comparative, evolutionary studies using site-mutagenesis, domain swapping and voltage-clamp techniques. On the basis of our new studies using a combination of ab initio structure prediction, 3D folding recognition by threading, homology modeling, molecular dynamics simulations and site-mutagenesis, we propose a new mechanism of how prestin interacts with intracellular anions to generate gating current and conformational change. Future research directions and potential application of prestin will also be discussed (Supported by NIH grant R01 DC 004696 from the NIDCD).
