SCN- induces prestin contraction through reduced intermonomer angles and a modified transporter like movement of each monomer.

Mariadasse, R.; Powers, M.; Bai, J.-P.; Zhang, C.; Subramaniya, S.; Yang, J.; Sigworth, F. J.; Sundaram, V. K.; Butan, C.; Beckstein, O.; Santos-Sacchi, J.; Navaratnam, D. S.

doi:10.64898/2026.10.28.762595

bioRxiv · 10.64898/2026.10.28.762595

SCN- induces prestin contraction through reduced intermonomer angles and a modified transporter like movement of each monomer.

Mariadasse, R.·Powers, M.·Bai, J.-P.·Zhang, C.·Subramaniya, S.·Yang, J.·Sigworth, F. J.·Sundaram, V. K.·Butan, C.·Beckstein, O.·Santos-Sacchi, J.·Navaratnam, D. S.

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Abstract

Prestin is the membrane based molecular motor responsible for outer hair cell electromotility that expands and contracts in response to transmembrane voltage. How voltage brings these about is unknown but cryoEM structures in the presence of ligands has led to the extrapolation of structures with the transporter cycle and its expansion contraction coupling. We find prestin to adopt novel increasingly contracted states that are brought about by a reduced intermonomer angles in the obligate dimers and a transmembrane contraction of each monomer at its cytoplasmic half in the presence of SCN-. These changes are associated with a loss in the intermonomer beta sheet at its N terminus. There is a hyperpolarizing shift in Vh along with increased affinity for SCN-. SCN- binding at the internal binding site likely cause the structural changes since they are reversed by SCN- displacement by salicylate.

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Mariadasse, R., Powers, M., Bai, J.-P., Zhang, C., Subramaniya, S., Yang, J., Sigworth, F. J., Sundaram, V. K., Butan, C., Beckstein, O., Santos-Sacchi, J., Navaratnam, D. S.. 2026-11-03. SCN- induces prestin contraction through reduced intermonomer angles and a modified transporter like movement of each monomer.. https://doi.org/10.64898/2026.10.28.762595

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