title: Structural insight into the transmembrane segments 3 and 4 of the hERG potassium channel.
abstract: The hERG (human ether-a-go-go related gene) potassium channel is a voltage-gated potassium channel containing an N-terminal domain, a voltage-sensor domain, a pore domain and a C-terminal domain. The transmembrane segment 4 (S4) is important for sensing changes of membrane potentials through positively charge residues. A construct containing partial S2-S3 linker, S3, S4 and the S4-S5 linker of the hERG channel was purified into detergent micelles. This construct exhibits good quality NMR spectrum when it was purified in lyso-myristoyl phosphatidylglycerol (LMPG) micelles. Structural study showed that S3 contains two short helices with a negatively charged surface. The S4 and S4-S5 linker adopt helical structures. The six positively charged residues in S4 localize at different sides, suggesting that they may have different functions in channel gating. Relaxation studies indicated that S3 is more flexible than S4. The boundaries of S3-S4 and S4-S4-S5 linker were identified. Our results provided structural information of the S3 and S4, which will be helpful to understand their roles in channel gating.
authors.affiliation: Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
authors.forename: Qingxin
authors.initials: Q
authors.lastname: Li
authors.forename: Ying Lei
authors.initials: YL
authors.lastname: Wong
authors.forename: Hui Qi
authors.initials: HQ
authors.lastname: Ng
authors.forename: Shovanlal
authors.initials: S
authors.lastname: Gayen
authors.forename: CongBao
authors.initials: C
authors.lastname: Kang
mesh_terms: D000595:Amino Acid Sequence; D002850:Chromatography, Gel; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry*; D008823:Micelles; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D008823:Micelles
keywords: NMR spectroscopy; S4 segment; hERG; potassium channel; voltage-gated potassium channel