Glutamate transporter homolog-based model predicts that anion-π interaction is the mechanism for the voltage-dependent response of prestin

Sándor Lovas, David Z. He, Huizhan Liu, Jie Tang, Jason L. Pecka, Marcus P D Hatfield, Kirk Beisel

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Prestin is the motor protein of cochlear outer hair cells. Its unique capability to perform direct, rapid, and reciprocal electromechanical conversion depends on membrane potential and interaction with intracellular anions. How prestin senses the voltage change and interacts with anions are still unknown. Our three-dimensional model of prestin using molecular dynamics simulations predicts that prestin contains eight transmem-brane-spanning segments and two helical re-entry loops and that tyrosyl residues are the structural specialization of the molecule for the unique function of prestin. Using site-directed mutagenesis and electrophysiological techniques, we confirmed that residues Tyr367, Tyr486, Tyr501, and Tyr508 contribute to anion binding, interacting with intracellular anions through novel anion-π interactions. Such weak interactions, sensitive to voltage and mechanical stimulation, confer prestin with a unique capability to perform electromechanical and mechanoelectric conversions with exquisite sensitivity. This novel mechanism is completely different from all known mechanisms seen in ion channels, transporters, and motor proteins.

Original languageEnglish
Pages (from-to)24326-24339
Number of pages14
JournalJournal of Biological Chemistry
Volume290
Issue number40
DOIs
StatePublished - Oct 2 2015

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Amino Acid Transport System X-AG
Anions
Electric potential
Outer Auditory Hair Cells
Mutagenesis
Reentry
Molecular Dynamics Simulation
Site-Directed Mutagenesis
Ion Channels
Membrane Potentials
Molecular dynamics
Proteins
Cells
Membranes
Molecules
Computer simulation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Glutamate transporter homolog-based model predicts that anion-π interaction is the mechanism for the voltage-dependent response of prestin. / Lovas, Sándor; He, David Z.; Liu, Huizhan; Tang, Jie; Pecka, Jason L.; Hatfield, Marcus P D; Beisel, Kirk.

In: Journal of Biological Chemistry, Vol. 290, No. 40, 02.10.2015, p. 24326-24339.

Research output: Contribution to journalArticle

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AU - He, David Z.

AU - Liu, Huizhan

AU - Tang, Jie

AU - Pecka, Jason L.

AU - Hatfield, Marcus P D

AU - Beisel, Kirk

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