Evidence for the Binding of Phosphate Ion to the C-Terminus Region in Aβ1-40 Using Heteronuclear NMR Analyses
Authors: Nagata-Uchiyama, Makiko; Abe, Yoshito; Monji, Akira; Kanba, Shigenobu; Ueda, Tadashi
Source: Protein and Peptide Letters, Volume 17, Number 2, February 2010 , pp. 176-180(5)
Publisher: Bentham Science Publishers
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.
Document Type: Research article
Publication date: 2010-02-01
- Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.