Evidence for the Binding of Phosphate Ion to the C-Terminus Region in Aβ1-40 Using Heteronuclear NMR Analyses

Title: Evidence for the Binding of Phosphate Ion to the C-Terminus Region in Aβ1-40 Using Heteronuclear NMR Analyses

Volume: 17 Issue: 2

Author(s): Makiko Nagata-Uchiyama, Yoshito Abe, Akira Monji, Shigenobu Kanba and Tadashi Ueda

Affiliation:

Keywords: Alzheimer's disease, amyloid beta peptide 1-40, chemical shift perturbation analysis, heteronuclear NMR, phosphate ion

Abstract: Amyloid fibril formation of amyloid beta peptide 1-40 (Aβ 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 Aβ 1-40 using chemical shift perturbation analysis of heteronuclear NMR. In titration analysis of 15N-labeled Aβ1-40 in the presence of 150 mM phosphate ion or 150 mM chloride ion, we identified the residues affected by these ions in Aβ 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 β-strand region in Aβ1-40. Therefore, we suggested that phosphate ions interacted with the potential β-strand region in Aβ1-40 to be hard to form β-sheet in Aβ 1-40, resulting in retardation of the amyloid fibril formation.

Cite this article as:

Nagata-Uchiyama Makiko, Abe Yoshito, Monji Akira, Kanba Shigenobu and Ueda Tadashi, Evidence for the Binding of Phosphate Ion to the C-Terminus Region in Aβ1-40 Using Heteronuclear NMR Analyses, Protein & Peptide Letters 2010; 17 (2) . https://dx.doi.org/10.2174/092986610790226058