Mapping of interactions between the amino and carboxy termini and the channel core in hERG K{+} channels

In this report, we analyzed by a site-directed cysteine and disulfide chemistry approach whether the eag/PAS and proximal domains at the hERG amino 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 the cysteines 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 cysteine at position 3 and an endogenous cysteine located at position 723 in the carboxy 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.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research