Serial perturbation of MinK in IKs implies an alpha-helical transmembrane span traversing the channel corpus.
I(Ks) channels contain four pore-forming KCNQ1 subunits and two accessory MinK subunits. MinK influences surface expression, voltage-dependence of gating, conduction, and pharmacology to yield the attributes characteristic of native channels in heart. The structure and location of the MinK transmembrane domain (TMD) remains a matter of scrutiny. As perturbation of gating analysis has correctly inferred the peripheral location and alpha-helical nature of TMDs in pore-forming subunits, the method is applied here to human MinK. Tryptophan and Asparagine substitution at 23 consecutive sites yields perturbation with alpha-helical periodicity (residues 44-56) followed by an alternating impact pattern (residues 56-63). Arginine substitution across the span suggests that as few as eight sites are occluded from aqueous solution (residues 50-57). We favor a TMD model that is alpha-helical with the external portion of the span at a lipid-protein boundary and the inner portion within the channel corpus in complex interactions.
Chen
Haijun
H
The Department of Pediatrics and Institute for Molecular Pediatric Sciences, Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA.
Goldstein
Steve A N
SA
D000818:Animals; D001216:Asparagine / Q000737:chemistry; D055592:Biophysical Phenomena; D001703:Biophysics; D002462:Cell Membrane / Q000378:metabolism; D004594:Electrophysiology / Q000379:methods; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008564:Membrane Potentials; D008968:Molecular Conformation; D009865:Oocytes / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000502:physiology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014364:Tryptophan / Q000737:chemistry; D014982:Xenopus laevis / Q000378:metabolism
C489622:KCNE1 protein, human; D008055:Lipids; D024642:Potassium Channels, Voltage-Gated; D001216:Asparagine; D014364:Tryptophan