Coupling between residues on S4 and S1 defines the voltage-sensor resting conformation in NaChBac.

Biophysical Journal
Tzur Paldi, Michael Gurevitz

Abstract

The voltage sensor is a four-transmembrane helix bundle (S1-S4) that couples changes in membrane potential to conformational alterations in voltage-gated ion channels leading to pore opening and ion conductance. Although the structure of the voltage sensor in activated potassium channels is available, the conformation of the voltage sensor at rest is still obscure, limiting our understanding of the voltage-sensing mechanism. By employing a heterologously expressed Bacillus halodurans sodium channel (NaChBac), we defined constraints that affect the positioning and depolarization-induced outward motion of the S4 segment. We compared macroscopic currents mediated by NaChBac and mutants in which E43 on the S1 segment and the two outermost arginines (R1 and R2) on S4 were substituted. Neutralization of the negatively charged E43 (E43C) had a significant effect on channel gating. A double-mutant cycle analysis of E43 and R1 or R2 suggested changes in pairing during channel activation, implying that the interaction of E43 with R1 stabilizes the voltage sensor in its closed/available state, whereas interaction of E43 with R2 stabilizes the channel open/unavailable state. These constraints on S4 dynamics that define its stepwise movemen...Continue Reading

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Citations

Nov 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Paul G DeCaenWilliam A Catterall
Dec 24, 2010·The Journal of Biological Chemistry·Takushi ShimomuraYoshinori Fujiyoshi
Apr 17, 2013·The Journal of General Physiology·James R Groome, Vern Winston
Jan 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·Adam ChamberlinH Peter Larsson
Apr 30, 2014·The Journal of General Physiology·Stephan A PlessChristopher A Ahern
Apr 23, 2014·Proceedings of the National Academy of Sciences of the United States of America·Annika F BarberManuel Covarrubias
May 15, 2012·Biochimica Et Biophysica Acta·Annika F BarberMichael L Klein
Jul 2, 2021·The Biochemical Journal·Boris S ZhorovKe Dong

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