A molecular clamp in the crystal structure of the N-terminal domain of the yeast Hsp90 chaperone

@article{Prodromou1997AMC,
  title={A molecular clamp in the crystal structure of the N-terminal domain of the yeast Hsp90 chaperone},
  author={Chrisostomos Prodromou and Stephen Mark Roe and Peter W Piper and Laurence H. Pearl},
  journal={Nature Structural Biology},
  year={1997},
  volume={4},
  pages={477-482}
}
Hsp90 is a highly specific chaperone for many signal transduction proteins, including steroid hormone receptors and a broad range of protein kinases. The crystal structure of the N-terminal domain of the yeast Hsp90 reveals a dimeric structure based on a highly twisted sixteen stranded β-sheet, whose topology suggests a possible 3D-domain-swapped structure for the intact Hsp90 dimer. The opposing faces of the β-sheets in the dimer define a potential peptide-binding cleft, suggesting that the N… 
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References

SHOWING 1-10 OF 50 REFERENCES
Structural Analysis of Substrate Binding by the Molecular Chaperone DnaK
TLDR
The crystal structure of a peptide complex with the substrate-binding unit of DnaK has been determined at 2.0 Å resolution, which suggests a model of conformation-dependent substrate binding that features a latch mechanism for maintaining long lifetime complexes.
Chaperone Function of Hsp90-Associated Proteins
TLDR
Results suggest the existence of a super-chaperone complex in the cytosol of eukaryotic cells and include members of the prolyl isomerase family.
The crystal structure of the bacterial chaperonln GroEL at 2.8 Å
The crystal structure of Escherichia coli GroEL shows a porous cylinder of 14 subunits made of two nearly 7-fold rotationally symmetrical rings stacked back-to-back with dyad symmetry. The subunits
Conformational activation of a basic helix-loop-helix protein (MyoD1) by the C-terminal region of murine HSP90 (HSP84).
TLDR
Results provide direct evidence that HSP90 can affect the conformational structure of a DNA-binding protein.
Molecular Chaperone Machines: Chaperone Activities of the Cyclophilin Cyp-40 and the Steroid Aporeceptor-Associated Protein p23
TLDR
In vitro folding assays showed that Cyp-40 and p23 functioned as molecular chaperones in a manner similar to that of Hsp90 or Hsp70, and both proteins interacted with the substrate to maintain a nonnative folding-competent intermediate.
A new member of the hsp90 family of molecular chaperones interacts with the retinoblastoma protein during mitosis and after heat shock
TLDR
Results suggest that Rb may be a physiological substrate for the hsp75 chaperone molecule, a heat shock protein that chaperones Rb, and identifies a mechanism, in addition to phosphorylation, by which Rb is regulated in response to progression of the cell cycle and to external stimuli.
Role of the protein chaperone YDJ1 in establishing Hsp90-mediated signal transduction pathways.
TLDR
Analysis of one of these substrates, the glucocorticoid receptor, indicated that Ydj1 exerts its effects through physical interaction with Hsp90 substrates.
Expression and crystallization of the yeast Hsp82 chaperone, and preliminary x‐ray diffraction studies of the amino‐terminal domain
TLDR
Expression of the Saccharomyces cerevisiae Hsp82 chaperone in a pep4‐3‐ and hsc82‐deficient strain of S. Cerevisiae yielded over 25% of the total cell protein as intact HSp82 as well as tetragonal bipyrimidal crystals of the amino‐terminal domain of H Sp82 under a variety of different conditions.
Hsp90 chaperones protein folding in vitro
TLDR
Hsp90 suppresses the formation of protein aggregates by binding to the target proteins at a stoichiometry of one Hsp90 dimer to one or two substrate molecule(s), and the yield of correctly folded and functional protein is increased significantly.
The carboxy-terminal region of mammalian HSP90 is required for its dimerization and function in vivo.
The majority of mouse HSP90 exists as alpha-alpha and beta-beta homodimers. Truncation of the 15-kDa carboxy-terminal region of mouse HSP90 by digestion with the Ca(2+)-dependent protease m-calpain
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5
...