The molecular chaperone Hsp104--a molecular machine for protein disaggregation.

@article{Bsl2006TheMC,
  title={The molecular chaperone Hsp104--a molecular machine for protein disaggregation.},
  author={Benjamin B{\"o}sl and Valerie Grimminger and Stefan Walter},
  journal={Journal of structural biology},
  year={2006},
  volume={156 1},
  pages={
          139-48
        }
}
At the Cold Spring Harbor Meeting on 'Molecular Chaperones and the Heat Shock Response' in May 1996, Susan Lindquist presented evidence that a chaperone of yeast termed Hsp104, which her group had been investigating for several years, is able to dissolve protein aggregates (Glover, J.R., Lindquist, S., 1998. Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94, 73-82). Among many of the participants this news stimulated reactions reaching from… Expand
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Elucidating the Interaction between the Molecular Chaperone Hsp104 and the Yeast Prion Sup35
TLDR
This thesis established that the middle (M) domain of Sup35 inhibited this process, while not affecting spontaneous fibrilization under non-inhibitory conditions, and suggested that the M-domain contains an Hsp104 binding site. Expand
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TLDR
The results reveal that ATP binding to NBD1 serves as a central regulatory switch for the chaperone; it triggers binding of polypeptides, and stimulates ATP hydrolysis in the C-terminal NBD2 by more than two orders of magnitude, implying that ATP hydroolysis in this domain is important for disaggregation. Expand
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Hspl04 functions in a manner not previously described for other heat-shock proteins: it mediates the resolubilization of heat-inactivated luciferase from insoluble aggregates. Expand
The Structure of ClpB A Molecular Chaperone that Rescues Proteins from an Aggregated State
TLDR
Taking together, mutagenesis and biochemical data show that both the relative position and motion of this coiled coil are critical for chaperone function, and propose a mechanism by which an ATP-driven conformational change is coupled to a large coiled-coil motion, which is indispensable for protein disaggregation. Expand
A Chaperone Pathway in Protein Disaggregation
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Hsp26 plays an important role in pathways that defend cells against environmental stress and the types of protein misfolding seen in neurodegenerative disease, and renders aggregates more accessible to Hsp104/Ssa1/Ydj1. Expand
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Chaperone-dependent disaggregation of chemically denatured aggregated luciferase showed that, similar to GFP disaggregation, incubation with Hsp70 results in the rapid start of the reactivation reaction. Expand
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TLDR
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TLDR
It is concluded that Hsp104 has a protein remodeling activity that acts on trapped, aggregated proteins and requires specific interactions with conventional chaperones to promote refolding of the intermediates it produces. Expand
Disassembling Protein Aggregates in the Yeast Cytosol
TLDR
It is shown that recovery of proteins from aggregates in the cell requires the chaperones to work together with defined but overlapping functions, and the results are consistent with a model of several interrelated defense lines against protein aggregation. Expand
Saccharomyces cerevisiae Hsp104 enhances the chaperone capacity of human cells and inhibits heat stress-induced proapoptotic signaling.
TLDR
It is established that Hsp104 shuttles across the nuclear envelope and enhances the chaperoning capacity of both the cytoplasm and nucleoplasm of intact cells, which establishes the fundamental properties of protein disaggregase function in human cells. Expand
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