Comparative study of the structure and interaction of the pore helices of the hERG and Kv1.5 potassium channels in model membranes.
The hERG channel is a voltage-gated potassium channel found in cardiomyocytes that contributes to the repolarization of the cell membrane following the cardiac action potential, an important step in the regulation of the cardiac cycle. The lipids surrounding K+channels have been shown to play a key role in their regulation, with anionic lipids shown to alter gating properties. In this study, we investigate how anionic lipids interact with the pore helix of hERG and compare the results with those from Kv1.5, which possesses a pore helix more typical of K+channels. Circular dichroism studies of the pore helix secondary structure reveal that the presence of the anionic lipid DMPS within the bilayer results in a slight unfolding of the pore helices from both hERG and Kv1.5, albeit to a lesser extent for Kv1.5. In the presence of anionic lipids, the two pore helices exhibit significantly different interactions with the lipid bilayer. We demonstrate that the pore helix from hERG causes significant perturbation to the order in lipid bicelles, which contrasts with only small changes observed for Kv1.5. These observations suggest that the atypical sequence of the pore helix of hERG may play a key role in determining how anionic lipids influence its gating.
Department of Chemistry, Université du Québec à Montréal, Downtown Station, PO Box 8888, Montreal, H3C 3P8, Canada.
Maïwenn
M
Beaugrand
Department of Chemistry, Université du Québec à Montréal, Downtown Station, PO Box 8888, Montreal, H3C 3P8, Canada.
Alexandre A
AA
Arnold
Department of Chemistry, Université du Québec à Montréal, Downtown Station, PO Box 8888, Montreal, H3C 3P8, Canada.
Steve
S
Bourgault
School of Biological Sciences, Highfield Campus, University of Southampton, Southampton, SO17 1BJ, UK.
Philip T F
PTF
Williamson
Department of Chemistry, Université du Québec à Montréal, Downtown Station, PO Box 8888, Montreal, H3C 3P8, Canada. marcotte.isabelle@uqam.ca.
Isabelle
http://orcid.org/0000-0001-7467-7119
I
Marcotte
D000595:Amino Acid Sequence; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D051666:Kv1.5 Potassium Channel / Q000737:chemistry* / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D017433:Protein Structure, Secondary
D051638:Ether-A-Go-Go Potassium Channels; D051666:Kv1.5 Potassium Channel; D008051:Lipid Bilayers
Bicelles; Circular dichroism; Dodecylphosphocholine; Ion channel; Lipids; Nuclear magnetic resonance