Interfacial gating triad is crucial for electromechanical transduction in voltage-activated potassium channels

Sandipan Chowdhury; Benjamin M Haehnel; Baron Chanda

doi:10.1085/jgp.201411185

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Interfacial gating triad is crucial for electromechanical transduction in voltage-activated potassium channels

Journal article

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Peer reviewed

Interfacial gating triad is crucial for electromechanical transduction in voltage-activated potassium channels

Sandipan Chowdhury, Benjamin M Haehnel and Baron Chanda

The Journal of general physiology, Vol.144(5), pp.457-467

11/2014

DOI: 10.1085/jgp.201411185

PMCID: PMC4210428

PMID: 25311635

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Abstract

Voltage-dependent potassium channels play a crucial role in electrical excitability and cellular signaling by regulating potassium ion flux across membranes. Movement of charged residues in the voltage-sensing domain leads to a series of conformational changes that culminate in channel opening in response to changes in membrane potential. However, the molecular machinery that relays these conformational changes from voltage sensor to the pore is not well understood. Here we use generalized interaction-energy analysis (GIA) to estimate the strength of site-specific interactions between amino acid residues putatively involved in the electromechanical coupling of the voltage sensor and pore in the outwardly rectifying KV channel. We identified candidate interactors at the interface between the S4-S5 linker and the pore domain using a structure-guided graph theoretical approach that revealed clusters of conserved and closely packed residues. One such cluster, located at the intracellular intersubunit interface, comprises three residues (arginine 394, glutamate 395, and tyrosine 485) that interact with each other. The calculated interaction energies were 3-5 kcal, which is especially notable given that the net free-energy change during activation of the Shaker KV channel is ∼14 kcal. We find that this triad is delicately maintained by balance of interactions that are responsible for structural integrity of the intersubunit interface while maintaining sufficient flexibility at a critical gating hinge for optimal transmission of force to the pore gate.

Amino Acid Sequence

Animals

Ion Channel Gating

Molecular Dynamics Simulation

Molecular Sequence Data

Protein Structure, Tertiary

Shaker Superfamily of Potassium Channels - chemistry

Static Electricity

Xenopus

Details

Title: Subtitle: Interfacial gating triad is crucial for electromechanical transduction in voltage-activated potassium channels
Creators: Sandipan Chowdhury - University of Wisconsin–Madison
Benjamin M Haehnel - University of Wisconsin–Madison
Baron Chanda - University of Wisconsin–Madison
Resource Type: Journal article
Publication Details: The Journal of general physiology, Vol.144(5), pp.457-467
DOI: 10.1085/jgp.201411185
PMID: 25311635
PMCID: PMC4210428
NLM abbreviation: J Gen Physiol
ISSN: 0022-1295
eISSN: 1540-7748
Grant note: R01 NS081293 / NINDS NIH HHS R01NS081293 / NINDS NIH HHS
Language: English
Date published: 11/2014
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9984297506302771

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