TY - JOUR T1 - Essential Helix Interactions in the Anion Transporter Domain of Prestin Revealed by Evolutionary Trace Analysis JF - The Journal of Neuroscience JO - J. Neurosci. SP - 12727 LP - 12734 DO - 10.1523/JNEUROSCI.2734-06.2006 VL - 26 IS - 49 AU - Lavanya Rajagopalan AU - Nimish Patel AU - Srinivasan Madabushi AU - Julie Anne Goddard AU - Venkat Anjan AU - Feng Lin AU - Cindy Shope AU - Brenda Farrell AU - Olivier Lichtarge AU - Amy L. Davidson AU - William E. Brownell AU - Fred A. Pereira Y1 - 2006/12/06 UR - http://www.jneurosci.org/content/26/49/12727.abstract N2 - Prestin, a member of the SLC26A family of anion transporters, is a polytopic membrane protein found in outer hair cells (OHCs) of the mammalian cochlea. Prestin is an essential component of the membrane-based motor that enhances electromotility of OHCs and contributes to frequency sensitivity and selectivity in mammalian hearing. Mammalian cells expressing prestin display a nonlinear capacitance (NLC), widely accepted as the electrical signature of electromotility. The associated charge movement requires intracellular anions reflecting the membership of prestin in the SLC26A family. We used the computational approach of evolutionary trace analysis to identify candidate functional (trace) residues in prestin for mutational studies. We created a panel of mutations at each trace residue and determined membrane expression and nonlinear capacitance associated with each mutant. We observe that several residue substitutions near the conserved sulfate transporter domain of prestin either greatly reduce or eliminate NLC, and the effect is dependent on the size of the substituted residue. These data suggest that packing of helices and interactions between residues surrounding the “sulfate transporter motif” is essential for normal prestin activity. ER -