In:
Biochemical Journal, Portland Press Ltd., Vol. 451, No. 3 ( 2013-05-01), p. 463-474
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.
Type of Medium:
Online Resource
ISSN:
0264-6021
,
1470-8728
Language:
English
Publisher:
Portland Press Ltd.
Publication Date:
2013
detail.hit.zdb_id:
1473095-9
SSG:
12
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