Helix-stabilizing effects of the pentapeptide KIFMK and its related peptides on the sodium channel inactivation gate peptides.
We have previously found by NMR and CD spectroscopic studies that the helical content of the sodium channel inactivation gate-related peptide (Ac-GGQDIFMTEEQK-NH2; MP-1A) in 80% trifluoroethanol solutions was increased by adding a pentapeptide, KIFMK. In order to study in further detail whether the presence of the IFM motif and the two lysine residues is a prerequisite for stabilizing the helical conformation, we examined interactions between various oligopeptides (RIFMR, KIFMTK, KIQMK, KAFAK, KIIIK) and MP-1A and its related peptides; that is, MP-2A in which Phe was replaced by Gln, MP-1MMA in which Thr was replaced by Met, MP-1TA in which Thr was removed from MP-1A, and MP-1A' in which L-Phe was replaced by D-Phe. It was found that the IFM motif was absolutely necessary in both the oligopeptide and the inactivation gate peptide. This finding means that hydrophobic interactions are operative between KIFMK and MP-1A. In contrast, KIFMK destabilized the helical structure of MP-1MMA, MP-1TA, and MP-1A', showing that the conformation around the IFM motif in the inactivation gate peptides is an important factor. It was concluded that the IFM motif and the two Lys residues are a prerequisite for effectively stabilizing the alpha-helix of MP-1A.
Maeda
Y
Y
Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Nakagawa
T
T
Kuroda
Y
Y
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D017386:Sequence Homology, Amino Acid; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000378:metabolism*; D014867:Water / Q000737:chemistry
D009842:Oligopeptides; D010455:Peptides; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C121919:lysyl-isoleucyl-phenylalanyl-methionyl-lysine; D014867:Water