Hsp70 chaperones: cellular functions and molecular mechanism.
Matthias P. Mayer,Bernd Bukau +1 more
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TLDR
This work has shown that for specific tasks the Hsp70 cycle is coupled to the action of other chaperones, such as Hsp90 and Hsp100, and this ATPase cycle is controlled by co-chaperones of the family of J-domain proteins, which target H Sp70s to their substrates, and by nucleotide exchange factors, which determine the lifetime of the HSp70-substrate complex.Abstract:
Hsp70 proteins are central components of the cellular network of molecular chaperones and folding catalysts. They assist a large variety of protein folding processes in the cell by transient association of their substrate binding domain with short hydrophobic peptide segments within their substrate proteins. The substrate binding and release cycle is driven by the switching of Hsp70 between the low-affinity ATP bound state and the high-affinity ADP bound state. Thus, ATP binding and hydrolysis are essential in vitro and in vivo for the chaperone activity of Hsp70 proteins. This ATPase cycle is controlled by co-chaperones of the family of J-domain proteins, which target Hsp70s to their substrates, and by nucleotide exchange factors, which determine the lifetime of the Hsp70-substrate complex. Additional co-chaperones fine-tune this chaperone cycle. For specific tasks the Hsp70 cycle is coupled to the action of other chaperones, such as Hsp90 and Hsp100.read more
Citations
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Synthesis and Evaluation of Novologues as C-Terminal Hsp90 Inhibitors with Cytoprotective Activity against Sensory Neuron Glucotoxicity
Bhaskar Reddy Kusuma,Liang Zhang,Sundstrom Teather,Laura B. Peterson,Rick T. Dobrowsky,Brian S. J. Blagg +5 more
TL;DR: It is identified that electronegative atoms placed at the meta-position of the B-ring exhibit improved cytoprotective activity, which is believed to result from favorable interactions with Lys539 in the Hsp90 C-terminal binding pocket.
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Exploring the limit of metazoan thermal tolerance via comparative proteomics: thermally induced changes in protein abundance by two hydrothermal vent polychaetes
TL;DR: Differences in how a mesotoleranceant and extremely thermotolerant eukaryote respond to thermal stress are revealed, and it is suggested that P. sulfincola's capacity to mitigate oxidative stress via increased synthesis of antioxidants and decreased flux through the mitochondrial electron transport chain enable pronounced thermotolerance.
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Beneficial effects of melatonin in protecting against cyclosporine A-induced cardiotoxicity are receptor mediated
Rita Rezzani,Luigi Fabrizio Rodella,Francesca Bonomini,Sandra Tengattini,Rossella Bianchi,Russel J. Reiter +5 more
TL;DR: Melatonin significantly reduces CsA cardiotoxicity, and the reduction in CsSA‐induced cardiot toxicity was mediated by the binding of melatonin to its membrane receptors.
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Chaperone effects on prion and nonprion aggregates.
TL;DR: This work has shown that functioning of the chaperones in reactivation of heat damaged proteins and in propagation of prions is based on the same molecular mechanisms but may lead to different consequences depending on the type of aggregate.
Journal ArticleDOI
Identification of an Allosteric Small-Molecule Inhibitor Selective for the Inducible Form of Heat Shock Protein 70
Matthew K. Howe,Khaldon Bodoor,David A. Carlson,Philip F. Hughes,Yazan Alwarawrah,David R. Loiselle,Alex M. Jaeger,David B. Darr,Jamie L. Jordan,Lucas Hunter,Eileen T. Molzberger,Theodore A Gobillot,Dennis J. Thiele,Jeffrey L. Brodsky,Neil L. Spector,Timothy A.J. Haystead +15 more
TL;DR: HS-72 is well-tolerated, showing bioavailability and efficacy, inhibiting tumor growth and promoting survival in a HER2+ model of breast cancer, suggesting an ideal starting point for a new generation of anticancer drugs targeting Hsp70i.
References
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Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein
TL;DR: Understanding how the thousands of different proteins synthesized in a cell use this chaperone machinery has profound implications for biotechnology and medicine.
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Hsp90 as a capacitor for morphological evolution
TL;DR: It is reported that when Drosophila Hsp90 is mutant or pharmacologically impaired, phenotypic variation affecting nearly any adult structure is produced, with specific variants depending on the genetic background and occurring both in laboratory strains and in wild populations.
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Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery.
William B. Pratt,David O. Toft +1 more
TL;DR: This purified system of five purified proteins should facilitate understanding of how eukaryotlc hsp70 and hsp90 work together as essential components of a process that alters the conformations of substrate proteins to states that respond in signal transduction.
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Invited Review: Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance
TL;DR: Recent evidence and hypotheses suggesting that the HSPs may be important modifying factors in cellular responses to a variety of physiologically relevant conditions such as hyperthermia, exercise, oxidative stress, metabolic challenge, and aging are examined.
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Hsp104, Hsp70, and Hsp40: A Novel Chaperone System that Rescues Previously Aggregated Proteins
John R Glover,Susan Lindquist +1 more
TL;DR: 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.