Structure of the pore-helix of the hERG K(+) channel

Pages, Guilhem, Torres, Allan M., Ju, Pengchu, Bansal, Paramjit, Alewood, Paul F., Kuchel, Philip W., and Vandenberg, Jamie L. (2009) Structure of the pore-helix of the hERG K(+) channel. European Biophysics Journal, 39 (1). pp. 111-120.

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The hERG K(+) channel undergoes rapid inactivation that is mediated by 'collapse' of the selectivity filter, thereby preventing ion conduction. Previous studies have suggested that the pore-helix of hERG may be up to seven residues longer than that predicted by homology with channels with known crystal structures. In the present work, we determined structural features of a peptide from the pore loop region of hERG (residues 600-642) in both sodium dodecyl sulfate (SDS) and dodecyl phosphocholine (DPC) micelles using NMR spectroscopy. A complete structure calculation was done for the peptide in DPC, and the localization of residues inside the micelles were analysed by using a water-soluble paramagnetic reagent with both DPC and SDS micelles. The pore-helix in the hERG peptide was only two-four residues longer at the N-terminus, compared with the pore helices seen in the crystal structures of other K(+) channels, rather than the seven residues suggested from previous NMR studies. The helix in the peptide spanned the same residues in both micellar environments despite a difference in the localization inside the respective micelles. To determine if the extension of the length of the helix was affected by the hydrophobic environment in the two types of micelles, we compared NMR and X-ray crystallography results from a homologous peptide from the voltage gated potassium channel, KcsA.

Item ID: 32528
Item Type: Article (Research - C1)
ISSN: 1432-1017
Keywords: Human ether-a-go-go related gene, NMR spectroscopy, paramagnetic relaxant reagent, voltage-gated potassium channels
Funders: National Health and Medical Research Council (NHMRC), Australian Research Council (ARC)
Projects and Grants: NHMRC Senior Research Fellowship 459401, ARC Professorial Fellowship DP034596, NHMRC grant No. 459402 , ARC grant DP0440808
Date Deposited: 26 Jun 2014 00:58
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110101 Medical Biochemistry: Amino Acids and Metabolites @ 100%
SEO Codes: 92 HEALTH > 9299 Other Health > 929999 Health not elsewhere classified @ 100%
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