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The subfamily-specific assembly of Eag and Erg K+ channels is determined by both the amino and the carboxyl recognition domains.

Authors: Lin, TF  Lin, IW  Chen, SC  Wu, HH  Yang, CS  Fang, HY  Chiu, MM  Jeng, CJ 
Citation: Lin TF, etal., J Biol Chem. 2014 Aug 15;289(33):22815-34. doi: 10.1074/jbc.M114.574814. Epub 2014 Jul 9.
Pubmed: (View Article at PubMed) PMID:25008323
DOI: Full-text: DOI:10.1074/jbc.M114.574814

A functional voltage-gated K(+) (Kv) channel comprises four pore-forming alpha-subunits, and only members of the same Kv channel subfamily may co-assemble to form heterotetramers. The ether-a-go-go family of Kv channels (KCNH) encompasses three distinct subfamilies: Eag (Kv10), Erg (Kv11), and Elk (Kv12). Members of different ether-a-go-go subfamilies, such as Eag and Erg, fail to form heterotetramers. Although a short stretch of amino acid sequences in the distal C-terminal section has been implicated in subfamily-specific subunit assembly, it remains unclear whether this region serves as the sole and/or principal subfamily recognition domain for Eag and Erg. Here we aim to ascertain the structural basis underlying the subfamily specificity of ether-a-go-go channels by generating various chimeric constructs between rat Eag1 and human Erg subunits. Biochemical and electrophysiological characterizations of the subunit interaction properties of a series of different chimeric and truncation constructs over the C terminus suggested that the putative C-terminal recognition domain is dispensable for subfamily-specific assembly. Further chimeric analyses over the N terminus revealed that the N-terminal region may also harbor a subfamily recognition domain. Importantly, exchanging either the N-terminal or the C-terminal domain alone led to a virtual loss of the intersubfamily assembly boundary. By contrast, simultaneously swapping both recognition domains resulted in a reversal of subfamily specificity. Our observations are consistent with the notion that both the N-terminal and the C-terminal recognition domains are required to sustain the subfamily-specific assembly of rat Eag1 and human Erg.

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RGD ID: 9693717
Created: 2015-02-12
Species: All species
Last Modified: 2015-02-12
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.