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

Yukiko Muroi; Manoel Arcisio-Miranda; Sandipan Chowdhury; Baron Chanda

doi:10.1038/nsmb.1749

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

Journal article

Open access

Peer reviewed

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

Yukiko Muroi, Manoel Arcisio-Miranda, Sandipan Chowdhury and Baron Chanda

Nature structural & molecular biology, Vol.17(2), pp.230-237

02/2010

DOI: 10.1038/nsmb.1749

PMCID: PMC2879147

PMID: 20118934

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https://www.ncbi.nlm.nih.gov/pmc/articles/2879147View

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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.

Allosteric Regulation

Amino Acid Sequence

Amino Acid Substitution - genetics

Fluorometry

Models, Biological

Models, Molecular

Molecular Sequence Data

Mutagenesis, Site-Directed

Patch-Clamp Techniques

Protein Structure, Tertiary

Sodium Channels - chemistry

Sodium Channels - genetics

Sodium Channels - metabolism

Details

Title: Subtitle: Molecular determinants of coupling between the domain III voltage sensor and pore of a sodium channel
Creators: Yukiko Muroi - University of Wisconsin–Madison
Manoel Arcisio-Miranda - University of Wisconsin–Madison
Sandipan Chowdhury - University of Wisconsin–Madison
Baron Chanda - University of Wisconsin–Madison
Resource Type: Journal article
Publication Details: Nature structural & molecular biology, Vol.17(2), pp.230-237
DOI: 10.1038/nsmb.1749
PMID: 20118934
PMCID: PMC2879147
NLM abbreviation: Nat Struct Mol Biol
ISSN: 1545-9993
eISSN: 1545-9985
Grant note: R01 GM084140 / NIGMS NIH HHS R01 GM084140-02 / NIGMS NIH HHS R01 GM084140-02S1 / NIGMS NIH HHS R01 GM084140-01 / NIGMS NIH HHS
Language: English
Date published: 02/2010
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9984297511902771

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