Main-chain mutagenesis reveals intrahelical coupling in an ion channel voltage-sensor

Daniel T Infield; Kimberly Matulef; Jason D Galpin; Kin Lam; Emad Tajkhorshid; Christopher A Ahern; Francis I Valiyaveetil

doi:10.1038/s41467-018-07477-3

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Main-chain mutagenesis reveals intrahelical coupling in an ion channel voltage-sensor

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Main-chain mutagenesis reveals intrahelical coupling in an ion channel voltage-sensor

Daniel T Infield, Kimberly Matulef, Jason D Galpin, Kin Lam, Emad Tajkhorshid, Christopher A Ahern and Francis I Valiyaveetil

Nature communications, Vol.9(1), pp.5055-10

11/29/2018

DOI: 10.1038/s41467-018-07477-3

PMCID: PMC6265297

PMID: 30498243

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Abstract

Membrane proteins are universal signal decoders. The helical transmembrane segments of these proteins play central roles in sensory transduction, yet the mechanistic contributions of secondary structure remain unresolved. To investigate the role of main-chain hydrogen bonding on transmembrane function, we encoded amide-to-ester substitutions at sites throughout the S4 voltage-sensing segment of Shaker potassium channels, a region that undergoes rapid, voltage-driven movement during channel gating. Functional measurements of ester-harboring channels highlight a transitional region between α-helical and 3 segments where hydrogen bond removal is particularly disruptive to voltage-gating. Simulations of an active voltage sensor reveal that this region features a dynamic hydrogen bonding pattern and that its helical structure is reliant upon amide support. Overall, the data highlight the specialized role of main-chain chemistry in the mechanism of voltage-sensing; other catalytic transmembrane segments may enlist similar strategies in signal transduction mechanisms.

Details

Title: Subtitle: Main-chain mutagenesis reveals intrahelical coupling in an ion channel voltage-sensor
Creators: Daniel T Infield - Department of Molecular Physiology and Biophysics, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, 52242, USA
Kimberly Matulef - Program in Chemical Biology, Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, 97239, OR, USA
Jason D Galpin - Department of Molecular Physiology and Biophysics, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, 52242, USA
Kin Lam - NIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
Emad Tajkhorshid - Department of Biochemistry, Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
Christopher A Ahern - Department of Molecular Physiology and Biophysics, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, 52242, USA. christopher-ahern@uiowa.edu
Francis I Valiyaveetil - Program in Chemical Biology, Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, 97239, OR, USA. valiyave@ohsu.edu
Resource Type: Journal article
Publication Details: Nature communications, Vol.9(1), pp.5055-10
DOI: 10.1038/s41467-018-07477-3
PMID: 30498243
PMCID: PMC6265297
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: England
Grant note: R01 GM122420 / NIGMS NIH HHS R24 NS104617 / NINDS NIH HHS U54 GM087519 / NIGMS NIH HHS R01 GM087546 / NIGMS NIH HHS R01 GM106569 / NIGMS NIH HHS P41 GM104601 / NIGMS NIH HHS
Language: English
Date published: 11/29/2018
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984070562202771

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