Tau agregasyonunun CCT3 ve CCT7 apikal etki alanları tarafından engellenmesi.

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The eukaryotic chaperonin containing t-complex polypeptide 1 (CCT/TRiC) is a molecular chaperone that assists protein folding in an ATP-driven manner. It consists of two stacked identical rings that are each made up of eight distinct subunits. Here, we show that the apical domains of subunits CCT3 and CCT7 from humans are strong inhibitors of tau aggregation, which is associated with several neurological disorders such as Alzheimer's and Parkinson's diseases. Kinetic analyses and negative-stain electron microscopy indicate that the mechanism of inhibition of tau aggregation by the apical domains of subunits CCT3 and CCT7 differ. Aggregation of tau alone, or in the presence of the apical domain of subunit CCT7, can be described by a fragmentation model whereas in the presence of the apical domain of subunit CCT3, it fits a saturating elongation and fragmentation mechanism. Coarse-grained molecular dynamics simulations show that tau interacts with different regions in the apical domains of subunits CCT3 and CCT7, in agreement with their different inhibition mechanisms.

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