Evidence for the binding of phosphate ion to the C-terminus region in Aβ 1-40 using heteronuclear NMR analyses

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 hetero-nuclear nmr. in titration analysis of 15n-labeled aβ 1-40 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 aβ 1-40. therefore,we suggested that phosphate ions interacted with the potential -strand region in aβ 1-40 to be hard to form β-sheet in aβ 1-40,resulting in retardation of the amyloid fibril formation. © 2010 bentham science publishers ltd.