Regulation of Hsp70 Chaperones by Co‐chaperones

Mayer, Mathias; Bukau, Bernd

doi:10.1002/9783527619498.ch48

Cited by 3 publications

(3 citation statements)

References 214 publications

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“…While the prokaryotic system has a single Hsp70, NEF, and J protein, the number of genes has expanded in eukaryotes. For example, the yeast genome codes for 14 Hsp70s, 20 J-proteins (Craig and Huang 2005), and 3 NEFs (Mayer and Bukau 2005). In humans, there are 13 Hsp70s, 50 J-proteins (Hsp40), and seven NEFs (Kampinga et al 2009).…”

mentioning

confidence: 99%

The remarkable multivalency of the Hsp70 chaperones

Zuiderweg

Hightower

Gestwicki

2017

Cell Stress and Chaperones

112

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Hsp70 proteins are key to maintaining intracellular protein homeostasis. To carry out this task, they employ a large number of cochaperones and adapter proteins. Here, we review what is known about the interaction between the chaperones and partners, with a strong slant toward structural biology. Hsp70s in general, and Hsc70 (HSPA8) in particular, display an amazing array of interfaces with their protein cofactors. We also review the known interactions between Hsp70s with lipids and with active compounds that may become leads toward Hsp70 modulation for treatment of a variety of diseases.

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mentioning

confidence: 99%

The remarkable multivalency of the Hsp70 chaperones

Zuiderweg

Hightower

Gestwicki

2017

Cell Stress and Chaperones

112

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“…HSP70 isoforms are composed of an N -terminal ATPase domain, which binds ATP ( 1 ) and hydrolyses it to ADP ( 2 ), a substrate-binding domain, and a C -terminal domain. − The presence of a peptide in the substrate binding domain stimulates the ATPase activity of HSP70, increasing its normally slow rate of ATP hydrolysis. HSP70 is a weak ATPase, and maximal activity requires cochaperones, such as HSP40 .…”

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confidence: 99%

Novel Adenosine-Derived Inhibitors of 70 kDa Heat Shock Protein, Discovered Through Structure-Based Design

et al. 2009

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The design and synthesis of novel adenosine-derived inhibitors of HSP70, guided by modeling and X-ray crystallographic structures of these compounds in complex with HSC70/BAG-1, is described. Examples exhibited submicromolar affinity for HSP70, were highly selective over HSP90, and some displayed potency against HCT116 cells. Exposure of compound 12 to HCT116 cells caused significant reduction in cellular levels of Raf-1 and Her2 at concentrations similar to that which caused cell growth arrest.

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“…The two most abundant classes of molecular chaperones are the Hsp70s and the Hsp60s. Although a well-characterized set of cochaperones and cofactors has been described for prokaryotic Hsp70s such as DnaK, their eukaryotic homolog, Hsc70, has been found to interact with a much larger set of proteins, including chaperones Hsp90, Hsp100 and Hsp110, nucleotide-exchange factors such as Bag-1 and HspBP1, and other proteins such as Hip, Hop and CHIP 29 .…”

Section: Discussionmentioning

confidence: 99%

The structure of CCT–Hsc70NBD suggests a mechanism for Hsp70 delivery of substrates to the chaperonin

Cuéllar

Martín‐Benito

Scheres

et al. 2008

Nat Struct Mol Biol

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Chaperones, a group of proteins that assist the folding of other proteins, seem to work in a coordinated manner. Two major chaperone families are heat-shock protein families Hsp60 and Hsp70. Here we show for the first time the formation of a stable complex between chaperonin-containing TCP-1 (CCT) and Hsc70, two eukaryotic representatives of these chaperone families. This interaction takes place between the apical domain of the CCTβ subunit and the nucleotide binding domain of Hsc70, and may serve to deliver the unfolded substrate from Hsc70 to the substrate binding region of CCT. We also show that a similar interaction does not occur between their prokaryotic counterparts GroEL and DnaK, suggesting that in eukarya the two types of chaperones have evolved to a concerted action that makes the folding task more efficient.

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Regulation of Hsp70 Chaperones by Co‐chaperones

Cited by 3 publications

References 214 publications

The remarkable multivalency of the Hsp70 chaperones

The remarkable multivalency of the Hsp70 chaperones

Novel Adenosine-Derived Inhibitors of 70 kDa Heat Shock Protein, Discovered Through Structure-Based Design

The structure of CCT–Hsc70NBD suggests a mechanism for Hsp70 delivery of substrates to the chaperonin

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