2N7G

Structure of the cyclic nucleotide-binding homology domain of the hERG channel

Summary for 2N7G

• Entry DOI: 10.2210/pdb2n7g/pdb
• NMR Information: BMRB: 25805
• Descriptor: Potassium voltage-gated channel subfamily H member 2 (1 entity in total)
• Functional Keywords: herg, cnbhd, ion channel, lqts2, membrane protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane ; Multi-pass membrane protein : Q12809
• Total number of polymer chains: 1
• Total formula weight: 17439.93

Authors

Li, Y.,Ng, H.,Li, Q.,Kang, C. (deposition date: 2015-09-10, release date: 2016-05-18, Last modification date: 2024-05-15)

Primary citation

Li, Y.,Ng, H.Q.,Li, Q.,Kang, C.
Structure of the Cyclic Nucleotide-Binding Homology Domain of the hERG Channel and Its Insight into Type 2 Long QT Syndrome
Sci Rep, 6:23712-23712, 2016

PubMed Abstract: The human ether-à-go-go related gene (hERG) channel is crucial for the cardiac action potential by contributing to the fast delayed-rectifier potassium current. Mutations in the hERG channel result in type 2 long QT syndrome (LQT2). The hERG channel contains a cyclic nucleotide-binding homology domain (CNBHD) and this domain is required for the channel gating though molecular interactions with the eag domain. Here we present solution structure of the CNBHD of the hERG channel. The structural study reveals that the CNBHD adopts a similar fold to other KCNH channels. It is self-liganded and it contains a short β-strand that blocks the nucleotide-binding pocket in the β-roll. Folding of LQT2-related mutations in this domain was shown to be affected by point mutation. Mutations in this domain can cause protein aggregation in E. coli cells or induce conformational changes. One mutant-R752W showed obvious chemical shift perturbation compared with the wild-type, but it still binds to the eag domain. The helix region from the N-terminal cap domain of the hERG channel showed unspecific interactions with the CNBHD.

PubMed: 27025590
DOI: 10.1038/srep23712

Experimental method

SOLUTION NMR