PNAS Plus Significance Statements The structured core domain of αB-crystallin can prevent amyloid fibrillation and associated toxicity
نویسندگان
چکیده
We find that the core domain of the human molecular chaperone αBcrystallin can function effectively in preventing protein aggregation and amyloid toxicity. The core domain represents only half the total sequence of the protein, but it is one of the most potent known inhibitors of the aggregation of amyloid-β, a process implicated in Alzheimer’s disease. We have determined high-resolution structures of this core domain and investigated its biophysical properties in solution. We find (pp. E1562– E1570) that the excised domain efficiently prevents amyloid aggregation and thereby reduces the toxicity of the resulting aggregates to cells. The structures of these domains that we present should represent useful scaffolds for the design of novel amyloid inhibitors.
منابع مشابه
The structured core domain of αB-crystallin can prevent amyloid fibrillation and associated toxicity.
Mammalian small heat-shock proteins (sHSPs) are molecular chaperones that form polydisperse and dynamic complexes with target proteins, serving as a first line of defense in preventing their aggregation into either amorphous deposits or amyloid fibrils. Their apparently broad target specificity makes sHSPs attractive for investigating ways to tackle disorders of protein aggregation. The two mos...
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