title: Effect of pH on the aggregate formation of a non-amyloid component (1-13).
abstract: The formation of aggregates including amyloid fibrils in the peptide fragment of non-amyloid-beta component (NAC(1-13)) was investigated under a variety of solution conditions. Two types of sample preparation method from neutral and acidic conditions were examined. Electron microscopy observation showed amorphous aggregates in the sample at pH 4.5 adjusted from the neutral condition. The CD and HPLC quantitative analyses indicated that the formation of the amorphous aggregate did not accompany a conformational conversion from a random coil in the sample solution. The analyses of pKa values determined by pH titration experiments in NMR spectroscopy indicated that the protonation of the carboxyl group of the N-terminal glutamic acid triggers the aggregation of NAC(1-13). On the other hand, electron microscopy observation showed that the samples at pH 2.2 and 4.5 adjusted from an initial pH of 2.2 form fibrils. A beta-structure was detected by CD spectroscopy in the 1 mM NAC(1-13) at pH 2.2 immediately after preparation. The CD analyses of samples at different concentrations and temperatures indicated that 1 mM NAC(1-13) immediately after preparation at pH 2.2 was oligomerized. The quantity of the beta-structure was increased depending on the Incubation time. The results strongly suggested that the beta-conformational oligomers play a critical role for the fibril nucleus.
authors.affiliation: Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, 1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Abe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakanishi
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins; D016874:Neurofibrillary Tangles / Q000737:chemistry; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D012995:Solubility; D012996:Solutions; D051843:Synucleins
chemical_list: D000682:Amyloid; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D012996:Solutions; D051843:Synucleins