Helix-stabilizing effects of the pentapeptide KIFMK and its related peptides on the sodium channel inactivation gate peptides

Citation
Y. Maeda et al., Helix-stabilizing effects of the pentapeptide KIFMK and its related peptides on the sodium channel inactivation gate peptides, J PEPT RES, 58(5), 2001, pp. 413-423
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF PEPTIDE RESEARCH
ISSN journal
1397-002X → ACNP
Volume
58
Issue
5
Year of publication
2001
Pages
413 - 423
Database
ISI
SICI code
1397-002X(200111)58:5<413:HEOTPK>2.0.ZU;2-H
Abstract
We have previously found by NMR and CD spectroscopic studies that the helic al content of the sodium channel inactivation gate-related peptide (Ac-GGQD IFMTEEQK-NH2; MP-1A) in 80% trifluoroethanol solutions was increased by add ing 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 var ious oligopeptides (RIFMR, KIFMTK, KIQMK, KAFAK, KIIIK) and MP-1A and its r elated peptides; that is, MP-2A in which Phe was replaced by Gln, MP-1MMA i n 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 inactivati on gate peptide. This finding means that hydrophobic interactions are opera tive between KIFMK and MP-1A. In contrast, KIFMK destabilized the helical s tructure of MP1-1MMA, MP-1TA, and MP-1A', showing that the conformation aro und 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 prerequ isite for effectively stabilizing the alpha -helix of MP-1A.