Channelpedia

PubMed 23418776


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv10.1 , Kv11.1



Title: Mapping of interactions between the N- and C-termini and the channel core in HERG K+ channels.

Authors: Pilar de la Peña, Angeles Machín, Jorge Fernández-Trillo, Pedro Domínguez, Francisco Barros

Journal, date & volume: Biochem. J., 2013 May 1 , 451, 463-74

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23418776


Abstract
The characteristic gating properties of the HERG [human eag (ether-a-go-go)-related gene] potassium channel determine its contribution to cardiac repolarization and in setting the electrical behaviour of a variety of cells. In the present study we analysed, using a site-directed cysteine and disulfide chemistry approach, whether the eag/PAS (Per/Arnt/Sim) and proximal domains at the HERG N-terminus exert a role in controlling the access of the N-terminal flexible tail to its binding site in the channel core for interaction with the gating machinery. Whereas the eag/PAS domain is necessary for disulfide bridging, plus the cysteine residues introduced at positions 3 and 542 of the HERG sequence, the presence of the proximal domain seems to be dispensable. The state-dependent formation of a disulfide bridge between Cys3 and an endogenous cysteine residue at position 723 in the C-terminal C-linker suggests that the N-terminal tail of HERG can also get into close proximity with the C-linker structures located at the bottom of helix S6. Therefore the intrinsic flexibility of the N-tail and its proximity to both the S4-S5 loop and the C-linker may dynamically contribute to the modulation of HERG channel gating.