DnaJ Recruits DnaK to Protein Aggregates

Acebrón, Sergio P.; Fernández‐Sáiz, Vanesa; Taneva, Stefka G.; Moro, Fernando; Muga, Arturo

doi:10.1074/jbc.m706189200

Cited by 47 publications

(48 citation statements)

References 59 publications

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“…It is also likely that the different prion proteins contain structural elements that affect how they are recognized as substrates by the chaperone machinery. In the bacterial system the homologous Hsp70 and Hsp40 components, DnaK and DnaJ, respectively, act first on protein aggregates and recruit the Hsp104 homolog ClpB (Acebron et al 2008). If the situation in yeast is analogous, then the Ssa proteins and Hsp40's could determine substrate recognition of the prions and initiate interaction of the machinery.…”

Section: Discussionmentioning

confidence: 99%

Functionally Redundant Isoforms of a Yeast Hsp70 Chaperone Subfamily Have Different Antiprion Effects

Sharma

Masison

2008

Genetics

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Section: Discussionmentioning

confidence: 99%

Functionally Redundant Isoforms of a Yeast Hsp70 Chaperone Subfamily Have Different Antiprion Effects

Sharma

Masison

2008

Genetics

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“…Crystals of one form (hereafter referred to as form A) belong to space group P2 1 The X-ray data set for the cryocooled form A crystal of the complex with the long peptide was collected to 2.5-Å resolution using a Rigaku MicroMax007 microfocus rotating anode generator, a Rigaku Raxis-IV imaging plate area detector, and an X-Stream 2000 cold-stream generator. This data set was processed and scaled using d*TREK (37).…”

Section: Methodsmentioning

confidence: 99%

Allosteric Coupling between the Lid and Interdomain Linker in DnaK Revealed by Inhibitor Binding Studies

Liebscher

Roujeinikova

2009

J Bacteriol

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The molecular chaperone DnaK assists protein folding and refolding, translocation across membranes, and regulation of the heat shock response. In Escherichia coli, the protein is a target for insect-derived antimicrobial peptides, pyrrhocoricins. We present here the X-ray crystallographic analysis of the E. coli DnaK substratebinding domain in complex with pyrrhocoricin-derived peptide inhibitors. The structures show that pyrrhocoricins act as site-specific, dual-mode (competitive and allosteric) inhibitors, occupying the substrate-binding tunnel and disrupting the latch between the lid and the ␤-sandwich. Our structural analysis revealed an allosteric coupling between the movements of the lid and the interdomain linker, identifying a previously unknown mechanism of the lid-mediated regulation of the chaperone cycle.DnaK is the bacterial molecular chaperone from the Hsp70 (70-kDa heat shock protein) family that assists many cellular processes involving proteins in their nonnative conformations, such as folding of newly synthesized proteins, protein translocation across membranes, refolding of misfolded and aggregated proteins, degradation of unstable proteins, and regulation of the heat shock response (for reviews, see references 10, 28, and 42). The chaperone function of DnaK is based on its ability to transiently bind to exposed stretches of hydrophobic residues in partially or fully unfolded proteins in an ATP-controlled fashion, thereby preventing aggregation and misfolding. DnaK recognizes short peptide sequences containing up to five consecutive hydrophobic residues (with leucine found frequently in the middle), flanked preferentially by basic residues (42, 43). The molecularchaperone activity is functionally linked with ATP hydrolysis; the substrate-binding and release cycle is driven by the switching between the ATP-bound state, with low affinity and a high exchange rate for substrates, and the ADP-bound state, with high affinity and a low exchange rate for substrates.In vivo, DnaK activity is supported by two cochaperones, GrpE, which facilitates the ADP/ATP exchange, and DnaJ, which stimulates ATP hydrolysis and thus aids the peptide capture (10,25,28,38,54). DnaJ itself also recognizes exposed stretches of hydrophobic residues in partially unfolded or denatured proteins, with specificity overlapping with that of DnaK (44). It is therefore thought that DnaJ serves as a scanning factor for DnaK by binding specific unfolded substrates and presenting them to the ATP-bound form of DnaK.Escherichia coli DnaK is composed of two domains: an Nterminal ATPase domain (residues 1 to 387) and a C-terminal substrate-binding domain (SBD) (residues 388 to 638) (10).The latter is made up of an 18-kDa ␤-sandwich subdomain that holds the substrate-binding cleft and a C-terminal ␣-helicalbundle "lid" subdomain that stabilizes the complex with the peptide substrate and controls the accessibility of the peptide binding site but does not interact with the substrate directly (5, 55). Removal of the lid subdomain by truncatio...

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“…The modulation of the ClpB disaggregase by DnaK was already established biochemically [49][50][51], but a recent study by the Kay lab determined the structural basis of ClpB-DnaK complex formation, revealing new insights into the actual disaggregase mechanism [48]. …”

Section: Clp Familymentioning

confidence: 99%

Chaperones and chaperone–substrate complexes: Dynamic playgrounds for NMR spectroscopists

Burmann¹,

Hiller²

2015

Progress in Nuclear Magnetic Resonance Spectroscopy

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DnaJ Recruits DnaK to Protein Aggregates

Cited by 47 publications

References 59 publications

Functionally Redundant Isoforms of a Yeast Hsp70 Chaperone Subfamily Have Different Antiprion Effects

Functionally Redundant Isoforms of a Yeast Hsp70 Chaperone Subfamily Have Different Antiprion Effects

Allosteric Coupling between the Lid and Interdomain Linker in DnaK Revealed by Inhibitor Binding Studies

Chaperones and chaperone–substrate complexes: Dynamic playgrounds for NMR spectroscopists

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