Department of Biochemistry, Molecular and Structural Biology, JoZef Stefan Institute, Jamova 39, Slovenia.
J Biol Chem. 2010 Jan 29;285(5):3201-10. doi: 10.1074/jbc.M109.024620. Epub 2009 Dec 2.
To contribute to the question of the putative role of cystatins in Alzheimer disease and in neuroprotection in general, we studied the interaction between human stefin B (cystatin B) and amyloid-beta-(1-40) peptide (Abeta). Using surface plasmon resonance and electrospray mass spectrometry we were able to show a direct interaction between the two proteins. As an interesting new fact, we show that stefin B binding to Abeta is oligomer specific. The dimers and tetramers of stefin B, which bind Abeta, are domain-swapped as judged from structural studies. Consistent with the binding results, the same oligomers of stefin B inhibit Abeta fibril formation. When expressed in cultured cells, stefin B co-localizes with Abeta intracellular inclusions. It also co-immunoprecipitates with the APP fragment containing the Abeta epitope. Thus, stefin B is another APP/Abeta-binding protein in vitro and likely in cells.
为了探讨胱抑素在阿尔茨海默病中的潜在作用以及在神经保护中的一般作用，我们研究了人源 stefin B（胱抑素 B）与淀粉样β肽（1-40）（Abeta）之间的相互作用。我们使用表面等离子体共振和电喷雾质谱技术，能够证明这两种蛋白质之间存在直接相互作用。作为一个有趣的新事实，我们表明 stefin B 与 Abeta 的结合具有寡聚体特异性。从结构研究判断，与 Abeta 结合的 stefin B 二聚体和四聚体是结构交换的。与结合结果一致，stefin B 的相同寡聚体抑制 Abeta 纤维形成。当在培养的细胞中表达时，stefin B 与 Abeta 细胞内包涵体共定位。它还与含有 Abeta 表位的 APP 片段共免疫沉淀。因此，stefin B 是体外和细胞内另一种 APP/Abeta 结合蛋白。
