Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding

Langer, Thomas; Lu, Chi Zen; Echols, Harrison; Flanagan, John M.; Hayer, M. K.; Hartl, F. Ulrich

doi:10.1038/356683a0

Cited by 947 publications

(748 citation statements)

References 64 publications

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“…The folding function of HSPs relates to their capacity to recognize the hydrophobic amino acid chains exposed by non native proteins, whereas the actual folding by the different HSPs occurs in various ways. HSP70 folds nascent polypeptides and releases them via con formational changes by HSP90 in the cytoplasm, with HSP60 assisting in the final folding of proteins in an enclosed cage 35,36 . The folding machinery is assisted by the small HSPs, which function as 'holdases' involv ing binding to unfolded proteins and assisting in their delivery to the 'foldases' (REFS 4,37).…”

Section: The Proteostasis Network Componentsmentioning

confidence: 99%

Proteostasis in cardiac health and disease

Henning

Brundel²

2017

Nat Rev Cardiol

140

126

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The worldwide increase in life expectancy gives rise to an increasing prevalence of cardiac diseases, which remain the leading cause of disability and death in the developed world [1][2][3] . Currently, the mechanisms under lying how ageing contributes to the initiation or acceler ation of cardiac diseases are essentially unresolved. Prevailing theories of ageing centre on gradual derail ment of cellular protein homeostasis -proteostasis -either by design (genetically) or by 'wear and tear' (environmentally) 3 . Central to the role of proteostasis derailment as a major factor in ageing is the observation that protein function declines over time.Proteins are the most versatile and complex macro molecules and are involved in the proper functioning of every biological process 4 . After synthesis as a poly peptide chain from the genetic code, proper function of a protein relies heavily on its correct folding into a 3D native state and on various post translational modifi cations, mostly involving the addition of chem ical groups (including phosphate, acetate, and carbo hydrate). Protein maturation, transport, and ultimately breakdown is monitored and supported by various classes of proteins, collectively called 'protein quality control' (PQC) [3][4][5] . Balanced proteostasis, therefore, depends on proper PQC and is crucial for cellular and organismal health 6 . The intricate network making up the PQC involves numerous proteins, of which the main players are the chaperones and their regula tors 4,7-9 (assisting in folding and refolding of proteins) and the pathways that clear irreversibly misfolded and aggregation prone proteins (the ubiquitin-proteasome system [UPS] and autophagy systems) 9-11 . With ageing, the gradual accumulation of misfolded or damaged pro teins, together with concomitant failure of PQC, results in proteotoxic stress and compromised defence against reactive oxygen species (ROS) 10 , a process that is likely to be accelerated in various age related diseases includ ing neurodegenerative diseases 12,13 , type 2 diabetes mel litus 14 , cancer 15 , and cardiac diseases [16][17][18][19][20] . In addition to the accumulation of misfolded proteins, ageing is accompanied by an imbalance in the proteome, as indi cated by lowered expression of chaperone, proteaso mal, ribosomal, and mitochondrial proteins, whereas proteins related to oxidative stress are upregulated 21,22 . Although mild impairment of proteostasis extends lifespan in Caenorhabditis elegans, referred to as hormesis, sustained impairment is accompanied by loss of PQC to neutralize this effect 3,5 . Importantly, evidence indicates that the amount of soluble, aggregate prone protein oligomers, rather than the abundance of pro tein aggregates, correlates with disease severity 23,24 . Therefore, protein aggregates, which contain both misfolded proteins and elevated levels of chaper ones, constitute an adequate PQC response, aimed at sequestering potentially harmful protein oligomers, rather than embodying the ultimate cellular threat 25 . This ...

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Section: The Proteostasis Network Componentsmentioning

confidence: 99%

Proteostasis in cardiac health and disease

Henning

Brundel²

2017

Nat Rev Cardiol

140

126

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“…To date, the majority of works that have been done on defi ned DnaK-DnaJ systems at a prokaryotic level has principally involved in the E. coli system [18][19][20][21][22]. A number of works have also been performed on other prokaryotic organisms [23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

A 70-kDa molecular chaperone, DnaK, from the industrial bacterium Bacillus licheniformis: gene cloning, purification and molecular characterization of the recombinant protein

et al. 2009

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The heat shock protein 70 (Hsp70/DnaK) gene of Bacillus licheniformis is 1,839 bp in length encoding a polypeptide of 612 amino acid residues. The deduced amino acid sequence of the gene shares high sequence identity with other Hsp70/DnaK proteins. The characteristic domains typical for Hsps/DnaKs are also well conserved in B. licheniformis DnaK (BlDnaK). BlDnaK was overexpressed in Escherichia coli using pQE expression system and the recombinant protein was purifi ed to homogeneity by nickel-chelate chromatography. The optimal temperature for ATPase activity of the purifi ed BlDnaK was 40°C in the presence of 100 mM KCl. The purifi ed BlDnaK had a V max of 32.5 nmol Pi/min and a K M of 439 μM. In vivo, the dnaK gene allowed an E. coli dnaK756-ts mutant to grow at 44°C, suggesting that BlDnaK should be functional for survival of host cells under environmental changes especially higher temperature. We also described the use of circular dichroism to characterize the conformation change induced by ATP binding. Binding of ATP was not accompanied by a net change in secondary structure, but ATP together with Mg 2+ and K + ions had a greater enhancement in the stability of BlDnaK at stress temperatures. Simultaneous addition of DnaJ, GrpE, and NR-peptide (NRLLLTG) synergistically stimulates the ATPase activity of BlDnaK by 11.7-fold.

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“…Mitochondrial hsp70 may stay associated with the preprotein until it is transferred to the hsp60 folding machinery (Cheng et al, 1989;Ostermann et al, 1989), a process which conceivably could require the cooperation of putative mitochondrial homologues of DnaJ and GrpE (Langer et al, 1992). Hsp60 seems to have a dual role in mitochondrial protein import: it functions in folding and assembly of imported proteins (Cheng et al, 1989).…”

Section: The Membrane Potential Hsp70 and Atp In The Matrix Are Essementioning

confidence: 99%

Mitochondrial protein import: Specific recognition and membrane translocation of preproteins

et al. 1993

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Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding

Cited by 947 publications

References 64 publications

Proteostasis in cardiac health and disease

Proteostasis in cardiac health and disease

A 70-kDa molecular chaperone, DnaK, from the industrial bacterium Bacillus licheniformis: gene cloning, purification and molecular characterization of the recombinant protein

Mitochondrial protein import: Specific recognition and membrane translocation of preproteins

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