Structure of the pore-helix of the hERG K(+) channel.
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.
Pages
Guilhem
G
School of Molecular and Microbial Biosciences, University of Sydney, Sydney, NSW, 2006, Australia.
Torres
Allan M
AM
Ju
Pengchu
P
Bansal
Paramjit S
PS
Alewood
Paul F
PF
Kuchel
Philip W
PW
Vandenberg
Jamie I
JI
D000595:Amino Acid Sequence; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D016062:Porosity; D017433:Protein Structure, Secondary; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry
D051638:Ether-A-Go-Go Potassium Channels; D008823:Micelles; D010767:Phosphorylcholine; D012967:Sodium Dodecyl Sulfate; C028810:dodecylphosphocholine