grpe

GrpE is a bacterial co-chaperone of the Hsp70 chaperone system, functioning as the nucleotide exchange factor for the DnaK (Hsp70) ATPase. It is a soluble cytosolic protein that forms a dimer and typically has a long, predominantly alpha-helical coiled-coil structure. The GrpE dimer provides a platform that docks with DnaK to facilitate ADP release and subsequent ATP binding, thereby resetting DnaK for another cycle of substrate interaction.

Mechanistically, DnaK cycles between low- and high-affinity states for substrates depending on its nucleotide state. GrpE binds to DnaK and promotes the release of bound ADP by inducing conformational changes in the nucleotide-binding domain, speeding up the nucleotide exchange. In conjunction with DnaJ, GrpE accelerates the overall chaperone cycle, supporting efficient folding of polypeptides, especially under proteotoxic stress such as elevated temperatures.

GrpE is part of the bacterial heat shock response and is broadly conserved across bacteria. In many organisms, grpE homologs form part of operons with dnaK and dnaJ or are co-regulated with heat shock genes. Eukaryotic organelles contain GrpE-like proteins (often called GrpEL1 and GrpEL2) that serve similar nucleotide-exchange functions for mitochondrial or chloroplast Hsp70 systems, reflecting the evolutionary conservation of this activity.

Biological significance includes essential contributions to proper protein folding, stress tolerance, and cell viability under heat or other proteotoxic conditions. GrpE’s role as a nucleotide exchange factor makes it a key regulator of the bacterial DnaK/DnaJ/GrpE chaperone network.