Molecular determinants of coupling between the domain III voltage sensor and pore of a sodium channel.

Nature Structural & Molecular Biology
Yukiko MuroiBaron Chanda

Abstract

In a voltage-dependent sodium channel, the activation of voltage sensors upon depolarization leads to the opening of the pore gates. To elucidate the principles underlying this conformational coupling, we investigated a putative gating interface in domain III of the sodium channel using voltage-clamp fluorimetry and tryptophan-scanning mutagenesis. Most mutations have similar energetic effects on voltage-sensor activation and pore opening. However, several mutations stabilized the activated voltage sensor while concurrently destabilizing the open pore. When mapped onto a homology model of the sodium channel, most localized to hinge regions of the gating interface. Our analysis shows that these residues are involved in energetic coupling of the voltage sensor to the pore when both are in resting and when both are in activated conformations, supporting the notion that electromechanical coupling in a voltage-dependent ion channel involves the movement of rigid segments connected by elastic hinges.

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Citations

Sep 29, 2011·Cellular and Molecular Life Sciences : CMLS·Mitchell Goldfarb
Oct 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sandipan Chowdhury, Baron Chanda
May 1, 2013·Proceedings of the National Academy of Sciences of the United States of America·Tanja Kalstrup, Rikard Blunck
Oct 13, 2010·The Journal of General Physiology·Manoel Arcisio-MirandaBaron Chanda
Apr 27, 2011·The Journal of General Physiology·Georges A Haddad, Rikard Blunck
Dec 14, 2011·The Journal of General Physiology·Sandipan Chowdhury, Baron Chanda
Nov 28, 2012·The Journal of General Physiology·Jérôme J LacroixFrancisco Bezanilla
Apr 17, 2013·The Journal of General Physiology·James R Groome, Vern Winston
Jul 17, 2013·The Journal of General Physiology·Deborah L CapesBaron Chanda
Apr 30, 2014·The Journal of General Physiology·Stephan A PlessChristopher A Ahern
Jun 18, 2014·The Journal of General Physiology·Daniel Sigg
May 2, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jérôme J LacroixFrancisco Bezanilla
Mar 27, 2012·Current Opinion in Structural Biology·Justin W Taraska
Dec 30, 2015·The Journal of General Physiology·Christopher A AhernBaron Chanda
Oct 15, 2014·The Journal of General Physiology·Sandipan ChowdhuryBaron Chanda
Mar 28, 2018·Nature Structural & Molecular Biology·Ana I Fernández-MariñoBaron Chanda
Aug 23, 2019·The Journal of General Physiology·John Cowgill, Baron Chanda
Dec 14, 2018·The Journal of General Physiology·Vinay IdikudaLei Zhou
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Dec 20, 2018·Circulation Research·Wandi ZhuJonathan R Silva
Sep 30, 2021·Proceedings of the National Academy of Sciences of the United States of America·Quinton BanksErick O Hernández-Ochoa

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