Molecular chaperones assist in protein folding by interacting with nascent polypeptide chains (NCs) during translation, but whether the ribosome can sense chaperone defects and abort translation of misfolding NCs has not been explored. Here we used quantitative proteomics in E. coli to investigate t...
The ATP-dependent chaperones of the Hsp70 class (DnaK in E. coli) function in protein folding in cooperation with J proteins and nucleotide exchange factors (DnaJ and GrpE in E. coli, respectively). Hsp70 prevents protein aggregation, increasing the folding yield, but whether it also enhances the ra...
Huntington's disease is a fatal neurodegenerative disorder characterized by the aggregation of polyglutamine-expanded huntingtin into oligomers and fibrils. How protein aggregation leads to cellular dysfunction is not well understood. To address this question, we combined in-cell single molecule flu...
The GroEL/GroES chaperonin mediates protein folding in bacteria in an ATP-dependent process. Studies in vitro show that the GroEL double-ring and the lid-shaped GroES transiently encapsulate unfolded protein for folding unimpaired by aggregation. To clarify critical aspects of this mechanism, we use...
Mammalian cells present a fingerprint of their proteome to the adaptive immune system through the display of endogenous peptides on MHC-I complexes. MHC-I peptides originate from protein degradation by the proteasome, suggesting that efficiently-folding, long-lived proteins could evade monitoring. H...
Manifestation of aggregate pathology in Huntington’s disease is thought to be facilitated by a preferential vulnerability of affected brain cells to age-dependent proteostatic decline. To understand how specific cellular backgrounds may facilitate pathologic aggregation, we utilized the yeast model ...
The interactome of fibrillar aggregates of the Tau repeat domain fused to YFP (TauRD-Y) was analyzed in HEK293T cells using SILAC. TauRD-Y was immunoprecipitated with anti-GFP antibody from lysates of SILAC-labeled cells expressing TauRD-Y in soluble form (light labeled; L), from cells containing ag...
The essential chaperonin TRiC/CCT mediates protein folding in cooperation with the co-chaperone prefoldin (PFD). As shown in vitro, the cylindrical TRiC complex facilitates folding through ATP-regulated client protein encapsulation. However, the functional dynamics of the chaperonin system in vivo r...
Data from ProteomeXchange, PXD ID: PXD001364. Experiment: AggregatesSILAC_DAF16_D01, file: 20110921_Velos3_DiWa_SA_Celegans_AggregatesSILAC_DAF16_D01-3.mzml. Published as part of Cell. 2015 May 7;161(4):919-932 . From the Abstract: {{i}} ... Here, we profiled more than 5, 000 proteins along the lif...
