publication . Article . Other literature type . 2014

Proline scan of the HERG channel S6 helix reveals the location of the intracellular pore gate.

Sheldon J. Clark; Stanislav Sokolov; Yen May Cheng; Yuki Abe; Tom W. Claydon; Samrat Thouta;
Open Access
  • Published: 01 Mar 2014 Journal: Biophysical Journal, volume 106, pages 1,057-1,069 (issn: 0006-3495, Copyright policy)
  • Publisher: Elsevier BV
Abstract
AbstractIn Shaker-like channels, the activation gate is formed at the bundle crossing by the convergence of the inner S6 helices near a conserved proline-valine-proline motif, which introduces a kink that allows for electromechanical coupling with voltage sensor motions via the S4-S5 linker. Human ether-a-go-go-related gene (hERG) channels lack the proline-valine-proline motif and the location of the intracellular pore gate and how it is coupled to S4 movement is less clear. Here, we show that proline substitutions within the S6 of hERG perturbed pore gate closure, trapping channels in the open state. Performing a proline scan of the inner S6 helix, from Ile655 ...
Subjects
free text keywords: Biophysics, Channels and Transporters, Linker, hERG, biology.protein, biology, Chemistry, Ether-A-Go-Go Potassium Channels, Stereochemistry, Gating, Intracellular, Helix, Electron transport chain, Xenopus, biology.organism_classification
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