Laboratorium für Physikalische Chemie, ETH Zürich, 8093 Zürich, Switzerland.
Angew Chem Int Ed Engl. 2010 May 25;49(23):3904-8. doi: 10.1002/anie.201000068.
Protein aggregates are both associated with disease and function. Because a variety of factors induce protein aggregation, a given protein can aggregate into different states. Here, we compare the structures and activities of five distinct protein aggregates of a single protein. Despite the diverse chemical, physical and biological treatments used to induce aggregation, all aggregate types contain the cross-β-sheet motif. However, they are structurally distinct, having different segments of the protein sequence involved in secondary structure formation. Because of these structural differences each aggregate has a unique set of properties. These include affinity to ATP, Thioflavin T, DNA, and membrane mimics, and interference with cell viability. The key to their multiple properties may be that the repetitive nature of the cross-β-sheet motif guarantees for many potent activities through cooperativity. The observed multidimensional structure-activity relationship of protein aggregates may be important for amyloid diseases but may also be advantageous in nanotechnology.
蛋白质聚集体与疾病和功能都有关联。由于各种因素都会诱导蛋白质聚集，因此一种给定的蛋白质可以聚集成不同的状态。在这里，我们比较了同一种蛋白质的五种不同蛋白质聚集体的结构和活性。尽管用于诱导聚集的化学、物理和生物学处理方法多种多样，但所有聚集体类型都含有交叉β-片层结构基序。然而，它们在结构上是不同的，涉及二级结构形成的蛋白质序列的不同片段。由于这些结构差异，每个聚集体都具有独特的一组性质。这些性质包括与 ATP、硫黄素 T、DNA 和膜类似物的亲和力，以及对细胞活力的干扰。它们具有多种性质的关键可能是，交叉β-片层结构基序的重复性保证了通过协同作用具有许多有效的活性。观察到的蛋白质聚集体的多维结构-活性关系对于淀粉样变性疾病可能很重要，但在纳米技术中也可能是有利的。
