Dataset Information

Essential helix interactions in the anion transporter domain of prestin revealed by evolutionary trace analysis.

ABSTRACT: 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.

SUBMITTER: Rajagopalan L

PROVIDER: S-EPMC2675645 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature

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Essential helix interactions in the anion transporter domain of prestin revealed by evolutionary trace analysis.

Rajagopalan Lavanya L Patel Nimish N Madabushi Srinivasan S Goddard Julie Anne JA Anjan Venkat V Lin Feng F Shope Cindy C Farrell Brenda B Lichtarge Olivier O Davidson Amy L AL Brownell William E WE Pereira Fred A FA

The Journal of neuroscience : the official journal of the Society for Neuroscience 20061201 49

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 ...[more]

PMID: 17151276

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Project description:The ion atmosphere is a critical structural, dynamic, and energetic component of nucleic acids that profoundly affects their interactions with proteins and ligands. Experimental methods that "count" the number of ions thermodynamically associated with the ion atmosphere allow dissection of energetic properties of the ion atmosphere, and thus provide direct comparison to theoretical results. Previous experiments have focused primarily on the cations that are attracted to nucleic acid polyanions, but have also showed that anions are excluded from the ion atmosphere. Herein, we have systematically explored the properties of anion exclusion, testing the zeroth-order model that anions of different identity are equally excluded due to electrostatic repulsion. Using a series of monovalent salts, we find, surprisingly, that the extent of anion exclusion and cation inclusion significantly depends on salt identity. The differences are prominent at higher concentrations and mirror trends in mean activity coefficients of the electrolyte solutions. Salts with lower activity coefficients exhibit greater accumulation of both cations and anions within the ion atmosphere, strongly suggesting that cation-anion correlation effects are present in the ion atmosphere and need to be accounted for to understand electrostatic interactions of nucleic acids. To test whether the effects of cation-anion correlations extend to nucleic acid kinetics and thermodynamics, we followed the folding of P4-P6, a domain of the Tetrahymena group I ribozyme, via single-molecule fluorescence resonance energy transfer in solutions with different salts. Solutions of identical concentration but lower activity gave slower and less favorable folding. Our results reveal hitherto unknown properties of the ion atmosphere and suggest possible roles of oriented ion pairs or anion-bridged cations in the ion atmosphere for electrolyte solutions of salts with reduced activity. Consideration of these new results leads to a reevaluation of the strengths and limitations of Poisson-Boltzmann theory and highlights the need for next-generation atomic-level models of the ion atmosphere.

Dataset Information

Essential helix interactions in the anion transporter domain of prestin revealed by evolutionary trace analysis.

Publications

Essential helix interactions in the anion transporter domain of prestin revealed by evolutionary trace analysis.

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