Hsp70 chaperones: cellular functions and molecular mechanism.
Matthias P. Mayer,Bernd Bukau +1 more
Reads0
Chats0
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
More filters
Journal ArticleDOI
Effects of iron loading on muscle: genome-wide mRNA expression profiling in the mouse
Alejandra Rodriguez,Mika Hilvo,Leena Kytömäki,Robert E. Fleming,Robert S. Britton,Bruce R. Bacon,Seppo Parkkila,Seppo Parkkila +7 more
TL;DR: Microarray analysis revealed iron-induced changes in the expression of several genes involved in the regulation of glucose and lipid metabolism, transcription and cellular stress responses that may represent novel connections between iron overload and pathological manifestations of HH such as cardiomyopathy and diabetes.
Journal ArticleDOI
Targeting the Proteostasis Network for Mycobacterial Drug Discovery.
TL;DR: The proteostasis network is explored as a noncanonical target for antibacterial drug discovery and provides protection from stresses and chemistries of host immunity by maintaining the integrity of the mycobacterial proteome.
Journal ArticleDOI
Oligomerization of a molecular chaperone modulates its activity.
TL;DR: It is shown that Trigger Factor (TF), an ATP-independent chaperone, exerts strikingly contrasting effects on the folding of non-native proteins as it transitions between a monomeric and a dimeric state.
Journal ArticleDOI
Prevention of autosomal dominant retinitis pigmentosa by systemic drug therapy targeting heat shock protein 90 (Hsp90)
Lawrence C. S. Tam,Anna-Sophia Kiang,Matthew Campbell,James Keaney,G. Jane Farrar,Marian M. Humphries,Paul F. Kenna,Peter Humphries +7 more
TL;DR: Treatment with the low-molecular-weight drug 17-allylamino-17-demethoxygeldanamycin (17-AAG), an ansamycin antibiotic that binds to heat shock protein Hsp90, activating a heat shock response in mammalian cells, protects photoreceptors against degeneration induced by aggregating mutant IMPDH1 protein, is shown to have the potential to suppress a wide range of mutant proteins causing RP.
Journal ArticleDOI
Laser vaccine adjuvants: History, progress, and potential
TL;DR: The most recent study utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines.
References
More filters
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.