InterPro domain: IPR009012

In prokaryotes, the nucleotide exchange factor GrpE and the chaperone DnaJ are required for nucleotide binding of the molecular chaperone DnaK [ 1 ]. The DnaK reaction cycle involves rapid peptide binding and release, which is dependent upon nucleotide binding. DnaJ accelerates the hydrolysis of ATP by DnaK, which enables the ADP-bound DnaK to tightly bind peptide. GrpE catalyses the release of ADP from DnaK, which is required for peptide release. In eukaryotes, GrpE is essential for mitochondrial Hsp70 function, however the cytosolic Hsp70 homologues are GrpE-independent.

GrpE binds as a homodimer to the ATPase domain of DnaK, and may interact with the peptide-binding domain of DnaK. GrpE accomplishes nucleotide exchange by opening the nucleotide-binding cleft of DnaK. GrpE is comprised of two domains, the N-terminal coiled coil domain, which may facilitate peptide release, and the C-terminal head domain, which forms part of the contact surface with the ATPase domain of DnaK. The head domain is comprised of six short beta strands with a limited hydrophobic core.

1. Crystal structure of the nucleotide exchange factor GrpE bound to the ATPase domain of the molecular chaperone DnaK. Science 276, 431-5