X-ray Crystallographic Structure of a Compact Dodecamer from a Peptide Derived from Aβ16-36
X-ray Crystallographic Structure of a Compact Dodecamer from a Peptide Derived from Aβ16-36
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DOI：
10.1021/acs.orglett.7b01445
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发表时间：
2017-07-07
期刊：
影响因子：
5.2
通讯作者：
Nowick, James S.
中科院分区：
文献类型：
--
作者：
Salveson, Patrick J.;Spencer, Ryan K.;Nowick, James S.
β-淀粉样肽A β组装成可溶性寡聚体与阿尔茨海默病的神经变性有关。A β寡聚体被认为是由β-发夹组成的。在这里，通过X射线晶体学探索了β-发夹的残基配对对形成的低聚物结构的影响。使用限制性大环β-发夹研究了三个残基配对，其中A β（30-36）与A β（17-23）、A β（16-22）和A β（15-21）并置。A β（16-22）-A β（30-36）配对形成由稠合的三角形三聚体组成的紧凑球形十二聚体。这种十二聚体可能有助于解释全长A β形成的三聚体和十二聚体的结构。
The assembly of the beta-amyloid peptide, A beta, into soluble oligomers is associated with neurodegeneration in Alzheimers disease. The A beta oligomers are thought to be composed of beta-hairpins. Here, the effect of shifting the residue pairing of the beta-hairpins on the structures of the oligomers that form is explored through X-ray crystallography. Three residue pairings were investigated using constrained macrocyclic beta-hairpins in which A beta(30-36) is juxtaposed with A beta(17-23), A beta(16-22), and A beta(15-21). The A beta(16-22)-A beta(30-36) pairing forms a compact ball-shaped dodecamer composed of fused triangular trimers. This dodecamer may help explain the structures of the trimers and dodecamers formed by full-length A beta.