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Insight into the molecular interaction between the cyclic nucleotide‐binding homology domain and the eag domain of the hERG channel
Author(s) -
Li Qingxin,
Ng Hui Qi,
Yoon Ho Sup,
Kang CongBao
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.05.056
Subject(s) - cyclic nucleotide binding domain , herg , linker , chemistry , transmembrane domain , biophysics , domain (mathematical analysis) , homology modeling , egf like domain , hamp domain , nucleotide , binding domain , binding site , gating , biochemistry , stereochemistry , potassium channel , biology , amino acid , gene , mathematical analysis , mathematics , computer science , enzyme , operating system
The gating of the hERG channel is regulated by its eag domain through molecular interaction with either the cyclic nucleotide‐binding homology domain (CNBHD) or the linker between transmembrane segments 4 and 5. Our NMR study on the purified CNBHD demonstrated that it contains nine β‐strands and does not bind cAMP. We show that the eag domain binds to the CBND through an interface containing several disease‐associated mutations. The N‐terminal cap domain and R56 in the eag domain are important for the interaction with the CNBHD. Residues from the CNBHD that were affected by the interaction with the eag domain were also identified. A R56Q mutation does not cause major structural changes in the eag domain and showed reduced interaction with the CNBHD.