Molecular basis for functional connectivity between the voltage sensor and the selectivity filter gate in shaker k+ channels

Carlos A.Z. Bassetto, João Luis Carvalho-De-souza, Francisco Bezanilla

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

In Shaker K+ channels, the S4-S5 linker couples the voltage sensor (VSD) and pore domain (PD). Another coupling mechanism is revealed using two W434F-containing channels: L361R:W434F and L366H:W434F. In L361R:W434F, W434F affects the L361R VSD seen as a shallower Q-V curve that crosses the G-V. In L366H:W434F, L366H relieves the W434F effect converting a non-conductive channel in a conductive one. We report a chain of residues connecting the VSD (S4) to the selectivity filter (SF) in the PD of an adjacent subunit as the molecular basis for voltage-sensor selectivity filter gate (VS-SF) coupling. Single alanine substitutions in this region (L409A, S411A, S412A or F433A) are enough to disrupt the VS-SF coupling, shown by the absence of Q-V and G-V crossing in L361R:W434F mutant and by the lack of ionic conduction in the L366H:W434F mutant. This residue chain defines a new coupling between the VSD and the PD in voltage-gated channels.

Original languageEnglish (US)
Article numbere63077
Pages (from-to)1-30
Number of pages30
JournaleLife
Volume10
DOIs
StatePublished - Feb 2021
Externally publishedYes

Keywords

  • C-type Inactivation
  • Cut-Open Voltage Clamp
  • Shaker K Channels
  • Voltage-Sensor Selectivity Filter Gate Coupling Mechanism
  • Voltage-gated ion channels
  • W434F Mutation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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