RT Journal Article SR Electronic T1 Essential Helix Interactions in the Anion Transporter Domain of Prestin Revealed by Evolutionary Trace Analysis JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 12727 OP 12734 DO 10.1523/JNEUROSCI.2734-06.2006 VO 26 IS 49 A1 Lavanya Rajagopalan A1 Nimish Patel A1 Srinivasan Madabushi A1 Julie Anne Goddard A1 Venkat Anjan A1 Feng Lin A1 Cindy Shope A1 Brenda Farrell A1 Olivier Lichtarge A1 Amy L. Davidson A1 William E. Brownell A1 Fred A. Pereira YR 2006 UL http://www.jneurosci.org/content/26/49/12727.abstract AB 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.