Structural transition of a 15 amino acid residue peptide induced by GM1.
The ganglioside GM1-binding peptide, p3, with a sequence of VWRLLAPPFSNRLLP, displayed a clear structural alteration depending on the presence or absence of GM1 micelles. The three-dimensional structures of the p3 peptide in the free and GM1 bound states were analyzed using two-dimensional NMR spectroscopic experiments with distance-restrained simulated annealing calculations. The NMR experiments for the p3 peptide alone indicated that the peptide has two conformers derived from the exchange of cis and trans forms at Pro(7)-Pro(8). Further study with theoretical modeling revealed that the p3 peptide has a curb conformation without regular secondary structure. On the other hand, the NMR studies for the p3 peptide with the GM1 micelles elucidated a trans conformer and gave a structure stabilized by hydrophobic interactions of beta- and helical turns. Based on these structural investigations, tryptophan, a core residue of the hydrophobic cluster, might be an essential residue for the recognition of the GM1 saccharides. The dynamic transition of the p3 peptide may play an important role in the function of GM1 as a multiple receptor as in the traditional pathway of the infection by cholera toxin.
Fujitani
Naoki
N
Division of Advanced Chemical Biology, Graduate School of Advanced Life Science, Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University, Sapporo 011-0021, Japan.
Shimizu
Hiroki
H
Matsubara
Teruhiko
T
Ohta
Takashi
T
Komata
Yuuki
Y
Miura
Nobuaki
N
Sato
Toshinori
T
Nishimura
Shin-Ichiro
S
D000595:Amino Acid Sequence; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000187:drug effects; D011487:Protein Conformation
D010455:Peptides; D005677:G(M1) Ganglioside