Evidence for the binding of phosphate ion to the C-terminus region in Abeta1-40 using heteronuclear NMR analyses.
Amyloid fibril formation of amyloid beta peptide 1-40 (Abeta 1-40) was reported to be retarded in the presence of 150mM phosphate buffer at pH 7 [Monji, Ustumi, Ueda, Imoto, Yoshida, Hashioka, Tashiro and Tashiro, J. Neurochemistry, 77, 1425-1432 (2007)]. In order to elucidate the reason why phosphate ion retards the amyloid fibril formation, we examined the preferential binding sites of phosphate ion to Abeta 1-40 using chemical shift perturbation analysis of heteronuclear NMR. In titration analysis of (15)N-labeled Abeta1-40 in the presence of 150 mM phosphate ion or 150 mM chloride ion, we identified the residues affected by these ions in Abeta 1-40. As a result, we found the tendency that phosphate ion preferentially bound to some residues located on the C-terminus region where the region was reported to be the potential beta-strand region in Abeta1-40. Therefore, we suggested that phosphate ions interacted with the potential beta-strand region in Abeta1-40 to be hard to form beta-sheet in Abeta 1-40, resulting in retardation of the amyloid fibril formation.
Nagata-Uchiyama
Makiko
M
Laboratory of Protein Structure, Function and Design, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Abe
Yoshito
Y
Monji
Akira
A
Kanba
Shigenobu
S
Ueda
Tadashi
T
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000682:Amyloid / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001665:Binding Sites; D002021:Buffers; D002712:Chlorides / Q000737:chemistry; D002942:Circular Dichroism; D008969:Molecular Sequence Data; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry
D000596:Amino Acids; D000682:Amyloid; D016229:Amyloid beta-Peptides; D002021:Buffers; D002712:Chlorides; D009587:Nitrogen Isotopes; D010446:Peptide Fragments; D010710:Phosphates; D011993:Recombinant Fusion Proteins; C078592:amyloid beta-protein (1-40)