Yan Yilin, Liu Jiajing, McCallum Scott A, Yang Daiwen, Wang Chunyu
Biology Department, Rensselear Polytechnic Institute, Troy, NY 12180, USA.
Biochem Biophys Res Commun. 2007 Oct 19;362(2):410-4. doi: 10.1016/j.bbrc.2007.07.198. Epub 2007 Aug 14.
To probe the role of side chain dynamics in Abeta aggregation, we studied the methyl dynamics of native Abeta40 and Abeta42 by measuring cross relaxation rates with interleaved data collection. The methyl groups in the C-terminus are in general more rigid in Abeta42 than in Abeta40, consistent with previous results from backbone (15)N dynamics. This lends support to the hypothesis that a rigid C-terminus in Abeta42 may serve as an internal aggregation seed. Interestingly, two methyl groups of V18 located in the central hydrophobic cluster are more mobile in Abeta42 than in Abeta40, most likely due to the paucity of V18 intra-molecular interactions in Abeta42. V18 may then be more available for inter-molecular interactions to form Abeta42 aggregates. Thus, the side chain mobility of the central hydrophobic cluster may play an important role in Abeta aggregation and may contribute to the difference in aggregation propensity between Abeta40 and Abeta42.
为了探究侧链动力学在β-淀粉样蛋白（Aβ）聚集过程中的作用，我们通过交错数据采集测量交叉弛豫率，研究了天然Aβ40和Aβ42的甲基动力学。与先前主链（15）N动力学的结果一致，Aβ42中C末端的甲基总体上比Aβ40中的更刚性。这支持了Aβ42中刚性C末端可能作为内部聚集种子的假说。有趣的是，位于中央疏水簇中的V18的两个甲基在Aβ42中比在Aβ40中更具流动性，这很可能是由于Aβ42中V18分子内相互作用较少。然后V18可能更易于进行分子间相互作用以形成Aβ42聚集体。因此，中央疏水簇的侧链流动性可能在Aβ聚集过程中起重要作用，并可能导致Aβ40和Aβ42之间聚集倾向的差异。
