Rubel Aleksandr A, Ryzhova Tatyana A, Antonets Kirill S, Chernoff Yury O, Galkin Alexey
St. Petersburg Branch of Vavilov Institute of Genetics (Russian Academy of Science); Universitetskaya nab. 7/9; St. Petersburg, Russia; Department of Genetics and Biotechnology; St. Petersburg State University; Universitetskaya nab. 7/9; St. Petersburg, Russia.
Prion. 2013 Nov-Dec;7(6):469-76. doi: 10.4161/pri.26867. Epub 2013 Oct 23.
Alzheimer disease is associated with the accumulation of oligomeric amyloid β peptide (Aβ), accompanied by synaptic dysfunction and neuronal death. Polymeric form of prion protein (PrP), PrP(Sc), is implicated in transmissible spongiform encephalopathies (TSEs). Recently, it was shown that the monomeric cellular form of PrP (PrP(C)), located on the neuron surface, binds Aβ oligomers (and possibly other β-rich conformers) via the PrP(23-27) and PrP(90-110) segments, acting as Aβ receptor. On the other hand, PrP(Sc) polymers efficiently bind to Aβ monomers and accelerate their oligomerization. To identify specific PrP sequences that are essential for the interaction between PrP polymers and Aβ peptide, we have co-expressed Aβ and PrP (or its shortened derivatives), fused to different fluorophores, in the yeast cell. Our data show that the 90-110 and 28-89 regions of PrP control the binding of proteinase-resistant PrP polymers to the Aβ peptide, whereas the 23-27 segment of PrP is dispensable for this interaction. This indicates that the set of PrP fragments involved in the interaction with Aβ depends on PrP conformational state.
阿尔茨海默病与寡聚淀粉样β肽（Aβ）的积累有关，同时伴有突触功能障碍和神经元死亡。朊病毒蛋白（PrP）的聚合形式PrP(Sc)与传染性海绵状脑病（TSEs）有关。最近的研究表明，位于神经元表面的单体细胞形式的PrP（PrP(C)）通过PrP(23 - 27)和PrP(90 - 110)片段与Aβ寡聚体（以及可能的其他富含β折叠的构象体）结合，充当Aβ受体。另一方面，PrP(Sc)聚合物能有效结合Aβ单体并加速其寡聚化。为了确定PrP聚合物与Aβ肽相互作用所必需的特定PrP序列，我们在酵母细胞中共表达了与不同荧光团融合的Aβ和PrP（或其缩短的衍生物）。我们的数据表明，PrP的90 - 110和28 - 89区域控制着蛋白酶抗性PrP聚合物与Aβ肽的结合，而PrP的23 - 27片段对于这种相互作用是可有可无的。这表明参与与Aβ相互作用的PrP片段集取决于PrP的构象状态。
