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Review
. 2003 Fall;8(3):218-24.
doi: 10.1379/1466-1268(2003)008<0218:ganeff>2.0.co;2.

GrpE, a nucleotide exchange factor for DnaK

Celia Harrison  1
Affiliations
Review

GrpE, a nucleotide exchange factor for DnaK

Celia Harrison. Cell Stress Chaperones. 2003 Fall.

Abstract

The cochaperone GrpE functions as a nucleotide exchange factor to promote dissociation of adenosine 5'-diphosphate (ADP) from the nucleotide-binding cleft of DnaK. GrpE and the DnaJ cochaperone act in concert to control the flux of unfolded polypeptides into and out of the substrate-binding domain of DnaK by regulating the nucleotide-bound state of DnaK. DnaJ stimulates nucleotide hydrolysis, and GrpE promotes the exchange of ADP for adenosine triphosphate (ATP) and also augments peptide release from the DnaK substrate-binding domain in an ATP-independent manner. The eukaryotic cytosol does not contain GrpE per se because GrpE-like function is provided by the BAG1 protein, which acts as a nucleotide exchange factor for cytosolic Hsp70s. GrpE, which plays a prominent role in mitochondria, chloroplasts, and bacterial cytoplasms, is a fascinating molecule with an unusual quaternary structure. The long alpha-helices of GrpE have been hypothesized to act as a thermosensor and to be involved in the decrease in GrpE-dependent nucleotide exchange that is observed in vitro at temperatures relevant to heat shock. This review describes the molecular biology of GrpE and focuses on the structural and kinetic aspects of nucleotide exchange, peptide release, and the thermosensor hypothesis.

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Figures

Fig 1.
Fig 1.
Ribbon drawings of dimeric GrpE bound to the adenosine triphosphatase (ATPase) domain of DnaK (PDB: 1DKG). GrpE monomers are colored blue and gold, and the ATPase domain is colored red. In the cocrystal structure, the connecting loops at the top of the 4-helix bundle were too disordered to be modeled. The unstructured N-terminal 33 amino acids of GrpE are drawn as a random coil. These residues have been implicated in interactions with the DnaK substrate-binding domain and were removed by proteolysis before crystallization. GrpE amino acids 34–39 were either unstructured (blue monomer) or too disordered to be modeled (gold monomer) in the cocrystal structure. The bottom of the long α-helices corresponds to residue 40 of GrpE. It can be seen that the compact β-sheet domain on the GrpE monomer proximal to DnaK sits at the top of the DnaK nucleotide-binding cleft, wedging it open. The figure on right is rotated by ∼70° about the vertical axis with respect to the figure on the left. These figures are rendered with “fog” to provide depth cueing. This figure was made with Molscript (Kraulis et al 1991), converted to a POVRAY-style format (D. Jeruzlami, unpublished software), and rendered with POVRAY (www.povray.org).
See this image and copyright information in PMC

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