Metazoan Hsp70-based protein disaggregases: emergence and mechanisms
نویسندگان
چکیده
منابع مشابه
Metazoan Hsp70-based protein disaggregases: emergence and mechanisms
Proteotoxic stresses and aging cause breakdown of cellular protein homeostasis, allowing misfolded proteins to form aggregates, which dedicated molecular machines have evolved to solubilize. In bacteria, fungi, protozoa and plants protein disaggregation involves an Hsp70•J-protein chaperone system, which loads and activates a powerful AAA+ ATPase (Hsp100) disaggregase onto protein aggregate sub...
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Accumulation of aggregation-prone misfolded proteins disrupts normal cellular function and promotes ageing and disease. Bacteria, fungi and plants counteract this by solubilizing and refolding aggregated proteins via a powerful cytosolic ATP-dependent bichaperone system, comprising the AAA+ disaggregase Hsp100 and the Hsp70-Hsp40 system. Metazoa, however, lack Hsp100 disaggregases. We show that...
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Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodeg...
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A baffling aspect of metazoan proteostasis is the lack of an Hsp104 ortholog that rapidly disaggregates and reactivates misfolded polypeptides trapped in stress induced disordered aggregates, preamyloid oligomers, or amyloid fibrils. By contrast, in bacteria, protozoa, chromista, fungi, and plants, Hsp104 orthologs are highly conserved and confer huge selective advantages in stress tolerance. M...
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ژورنال
عنوان ژورنال: Frontiers in Molecular Biosciences
سال: 2015
ISSN: 2296-889X
DOI: 10.3389/fmolb.2015.00057