A common pathway for detergent-assisted oligomerization of Aβ42.
A common pathway for detergent-assisted oligomerization of Aβ42.
复制标题
Aβ42去污剂辅助寡聚化的常见途径。
DOI：
10.1038/s42003-023-05556-w
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发表时间：
2023-11-21
影响因子：
5.9
通讯作者：
Zhou, Huan-Xiang
中科院分区：
文献类型：
--
作者：
Muhammedkutty, Fidha Nazreen Kunnath;Prasad, Ramesh;Gao, Yuan;Sudarshan, Tarunya Rao;Robang, Alicia S;Watzlawik, Jens O;Rosenberry, Terrone L;Paravastu, Anant K;Zhou, Huan-Xiang
淀粉样蛋白（a β）聚集是一个缓慢的过程，没有播种或辅助成核。十二烷基硫酸钠（SDS）胶束稳定a - β42小聚物（在二聚体到四聚体范围内）；随后SDS去除得到150-kD a - β42低聚物。十二烷基磷酸胆碱（DPC）胶束也稳定a - β42四聚体。本文通过固体核磁共振光谱和分子动力学模拟研究了洗涤剂辅助寡聚化途径。SDS和dpc诱导的低聚物具有相同的结构，这意味着它们具有共同的低聚途径。由c端区形成的反平行β片是SDS和DPC胶束中唯一稳定的结构，直接结合到150-kD低聚物中。三个Gly残基（位置33、37和38）形成了由SDS和DPC碳氢化合物尾部填充的孔，从而将潜在的不稳定特征转变为稳定因素。这些观察结果对细胞界面的内源性Aβ聚集具有启示意义。一项结合固态核磁共振波谱和分子动力学模拟的研究揭示了A - β42在洗涤剂辅助下寡聚的共同途径。
Amyloid beta (Aβ) aggregation is a slow process without seeding or assisted nucleation. Sodium dodecyl sulfate (SDS) micelles stabilize Aβ42 small oligomers (in the dimer to tetramer range); subsequent SDS removal leads to a 150-kD Aβ42 oligomer. Dodecylphosphorylcholine (DPC) micelles also stabilize an Aβ42 tetramer. Here we investigate the detergent-assisted oligomerization pathway by solid-state NMR spectroscopy and molecular dynamics simulations. SDS- and DPC-induced oligomers have the same structure, implying a common oligomerization pathway. An antiparallel β-sheet formed by the C-terminal region, the only stable structure in SDS and DPC micelles, is directly incorporated into the 150-kD oligomer. Three Gly residues (at positions 33, 37, and 38) create holes that are filled by the SDS and DPC hydrocarbon tails, thereby turning a potentially destabilizing feature into a stabilizing factor. These observations have implications for endogenous Aβ aggregation at cellular interfaces. A study jointly using solid-state NMR spectroscopy and molecular dynamics simulations reveals a common pathway for the detergent-assisted oligomerization of Aβ42.