Department of Biological Chemistry, University of California Los Angeles (UCLA), Howard Hughes Medical Institute (HHMI), Los Angeles, CA 90095, USA.
Science. 2012 Mar 9;335(6073):1228-31. doi: 10.1126/science.1213151.
Amyloid diseases, including Alzheimer's, Parkinson's, and the prion conditions, are each associated with a particular protein in fibrillar form. These amyloid fibrils were long suspected to be the disease agents, but evidence suggests that smaller, often transient and polymorphic oligomers are the toxic entities. Here, we identify a segment of the amyloid-forming protein αB crystallin, which forms an oligomeric complex exhibiting properties of other amyloid oligomers: β-sheet-rich structure, cytotoxicity, and recognition by an oligomer-specific antibody. The x-ray-derived atomic structure of the oligomer reveals a cylindrical barrel, formed from six antiparallel protein strands, that we term a cylindrin. The cylindrin structure is compatible with a sequence segment from the β-amyloid protein of Alzheimer's disease. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers.
淀粉样疾病，包括阿尔茨海默病、帕金森病和朊病毒病，每种疾病都与纤维形式的特定蛋白质有关。这些淀粉样纤维长期以来一直被怀疑是致病因子，但有证据表明，更小、通常是短暂和多态的低聚物是毒性实体。在这里，我们鉴定了淀粉样形成蛋白 αB 晶体蛋白的一个片段，该片段形成具有其他淀粉样低聚物特性的寡聚复合物：富含β-折叠的结构、细胞毒性和被寡聚体特异性抗体识别。寡聚物的 X 射线衍生原子结构揭示了一个由六个反平行蛋白质链形成的圆柱形桶，我们称之为圆柱蛋白。圆柱蛋白结构与阿尔茨海默病β-淀粉样蛋白的一段序列兼容。圆柱蛋白为迄今难以捉摸的淀粉样低聚物结构提供了模型。
