Structural study of the sodium channel inactivation gate peptide includingan isoleucine-phenylalanine-methionine motif and its analogous peptide (phenylalanine/glutamine) in trifluoroethanol solutions and SDS micelles

Citation
Y. Kuroda et al., Structural study of the sodium channel inactivation gate peptide includingan isoleucine-phenylalanine-methionine motif and its analogous peptide (phenylalanine/glutamine) in trifluoroethanol solutions and SDS micelles, J PEPT RES, 56(3), 2000, pp. 172-184
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF PEPTIDE RESEARCH
ISSN journal
1397-002X → ACNP
Volume
56
Issue
3
Year of publication
2000
Pages
172 - 184
Database
ISI
SICI code
1397-002X(200009)56:3<172:SSOTSC>2.0.ZU;2-T
Abstract
In order to gain insight into the gating mechanisms of Na+ channels, in par ticular their inactivation mechanisms, we studied the structures of the Na channel inactivation gate related peptide which includes the IFM (Ile-Phe- Met) motif (AcKKKFGGQDIFMTEEQKK-NH2; K1480-K1496 in rat brain type-IIA Nachannels, MP-3A) and its F/Q(Gln) substituted one (MP-4A) in trifluoroethan ol (TFE) solutions and sodium dodecyl sulfate (SDS) micelles using circular dichroism (CD) and H-1-NMR spectroscopies. Based on observed nuclear Overh auser effect constraints, three-dimensional structures of MP-3A and MP-4A w ere determined using simulated annealing molecular dynamics/energy minimiza tion calculations. In TFE solutions, no appreciable differences in the stru cture were observed using either CD or NMR spectra. In SDS micelles, howeve r, the two peptides exhibited definitely different structures from each oth er. It was found that in MP-3A, residues I1488 and T1491 were spatially pro ximate with each other owing to hydrogen bonding between the amide proton o f I1488 and the hydroxyl oxygen atom of T1491, whereas in MP-4A, F/Q substi tution separated them owing to conformational changes. The solvent-accessib le surfaces calculated for the structures of MP-3A and MP-4A showed that th e former has a smoother interaction surface to the hydrophobic docking site than the latter. In conclusion, the conformational changes, as well as dec reased hydrophobicity around the IFM motif owing to the F/Q mutation, may b e one reason why F1489Q mutated channels cannot inactivate almost completel y.