Correction to "β-Hairpin Alignment Alters Oligomer Formation in Aβ-Derived Peptides".
Correction to "β-Hairpin Alignment Alters Oligomer Formation in Aβ-Derived Peptides".
复制标题
更正“β 发夹排列改变 Aβ 衍生肽中的寡聚体形成”。
DOI：
10.1021/acs.biochem.4c00037
复制
发表时间：
2024
期刊：
影响因子：
2.9
通讯作者：
Nowick,JamesS
中科院分区：
文献类型：
--
作者：
Ruttenberg,SarahM;Kreutzer,AdamG;Truex,NicholasL;Nowick,JamesS
β淀粉样蛋白（Aβ）形成异质寡聚体，参与阿尔茨海默病（AD）的发病机制。许多Aβ寡聚体由β-发夹结构单元组成，即β-发夹构象的Aβ肽。Aβ的β-发夹可以采用多种比对，但β-发夹比对在Aβ寡聚体的形成和异质性中所起的作用知之甚少。为了探讨β-发夹序列对Aβ肽寡聚化的影响，我们设计并研究了两种不同β-发夹序列的模型肽。肽Aβm17- 36和Aβm17- 35分别模拟Aβ可以形成的两种不同的β-发夹，Aβ17- 36和Aβ17-35β-发夹。这些发夹在组成上相似，但在发夹排列上不同，改变了它们所含残基侧链的表面排列。X射线晶体学和SDS-PAGE表明，这些肽之间的面排列的差异导致不同的寡聚体形成。在晶体状态下，Aβm17- 36形成三角形三聚体，进一步组装形成六聚体，而Aβm17- 35形成四聚体β-桶。在SDS-PAGE中，Aβm17- 36组装形成梯状寡聚体，而Aβm17- 35组装形成二聚体或根本不组装。Aβm17- 36和Aβm17- 35行为的差异表明β-发夹排列是观察到的Aβ寡聚体异质性的来源。
Amyloid-β (Aβ) forms heterogeneous oligomers, which are implicated in the pathogenesis of Alzheimer’s disease (AD). Many Aβ oligomers consist of β-hairpin building blocks─Aβ peptides in β-hairpin conformations. β-Hairpins of Aβ can adopt a variety of alignments, but the role that β-hairpin alignment plays in the formation and heterogeneity of Aβ oligomers is poorly understood. To explore the effect of β-hairpin alignment on the oligomerization of Aβ peptides, we designed and studied two model peptides with two different β-hairpin alignments. Peptides Aβm17–36and Aβm17–35mimic two different β-hairpins that Aβ can form, the Aβ17–36and Aβ17–35β-hairpins, respectively. These hairpins are similar in composition but differ in hairpin alignment, altering the facial arrangements of the side chains of the residues that they contain. X-ray crystallography and SDS-PAGE demonstrate that the difference in facial arrangement between these peptides leads to distinct oligomer formation. In the crystal state, Aβm17–36forms triangular trimers that further assemble to form hexamers, while Aβm17–35forms tetrameric β-barrels. In SDS-PAGE, Aβm17–36assembles to form a ladder of oligomers, while Aβm17–35either assembles to form a dimer or does not assemble at all. The differences in the behavior of Aβm17–36and Aβm17–35suggest β-hairpin alignment as a source of the observed heterogeneity of Aβ oligomers.