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 Valiyaveetil

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 310 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.

Original languageEnglish (US)
Article number5055
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

mutagenesis
Mutagenesis
Hydrogen Bonding
Ion Channels
Amides
Shaker Superfamily of Potassium Channels
Esters
Hydrogen bonds
sensors
Sensors
Electric potential
electric potential
amides
esters
Hydrogen
Signal Transduction
Membrane Proteins
proteins
Signal transduction
decoders

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Main-chain mutagenesis reveals intrahelical coupling in an ion channel voltage-sensor. / Infield, Daniel T.; Matulef, Kimberly; Galpin, Jason D.; Lam, Kin; Tajkhorshid, Emad; Ahern, Christopher A.; Valiyaveetil, Francis.

In: Nature Communications, Vol. 9, No. 1, 5055, 01.12.2018.

Research output: Contribution to journalArticle

Infield DT, Matulef K, Galpin JD, Lam K, Tajkhorshid E, Ahern CA et al. Main-chain mutagenesis reveals intrahelical coupling in an ion channel voltage-sensor. Nature Communications. 2018 Dec 1;9(1). 5055. https://doi.org/10.1038/s41467-018-07477-3
Infield, Daniel T. ; Matulef, Kimberly ; Galpin, Jason D. ; Lam, Kin ; Tajkhorshid, Emad ; Ahern, Christopher A. ; Valiyaveetil, Francis. / Main-chain mutagenesis reveals intrahelical coupling in an ion channel voltage-sensor. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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