Acharya Srabasti, Srivastava Kinshuk R, Nagarajan Sureshbabu, Lapidus Lisa J
Department of Physics and Astronomy, Michigan State University, 567 Wilson Rd. Rm 4227, East Lansing, MI, 48824, USA.
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
Chemphyschem. 2016 Nov 4;17(21):3470-3479. doi: 10.1002/cphc.201600706. Epub 2016 Sep 15.
The rate of reconfiguration-or intramolecular diffusion-of monomeric Alzheimer (Aβ) peptides is measured and, under conditions that aggregation is more likely, peptide diffusion slows down significantly, which allows bimolecular associations to be initiated. By using the method of Trp-Cys contact quenching, the rate of reconfiguration is observed to be about five times faster for Aβ , which aggregates slowly, than that for Aβ , which aggregates quickly. Furthermore, the rate of reconfiguration for Aβ speeds up at higher pH, which slows aggregation, and in the presence of the aggregation inhibitor curcumin. The measured reconfiguration rates are able to predict the early aggregation behavior of the Aβ peptide and provide a kinetic basis for why Aβ is more prone to aggregation than Aβ , despite a difference of only two amino acids.
对单体阿尔茨海默病（Aβ）肽的重排速率（即分子内扩散速率）进行了测量，发现在更易发生聚集的条件下，肽扩散显著减慢，这使得双分子缔合得以启动。通过使用色氨酸 - 半胱氨酸接触猝灭法，观察到聚集缓慢的Aβ的重排速率比聚集迅速的Aβ快约五倍。此外，Aβ的重排速率在较高pH值（这会减缓聚集）以及存在聚集抑制剂姜黄素的情况下会加快。所测得的重排速率能够预测Aβ肽的早期聚集行为，并为尽管Aβ和Aβ仅相差两个氨基酸，但Aβ为何比Aβ更易于聚集提供了动力学依据。
