DnaK co-chaperone, GrpE
Thermus thermophilus HB8 (thermophilic bacteria)
Protein folding and quality control is necessary to express and maintain inherent functions of proteins. Hsp70 chaperone proteins play important roles in protein folding of nascent polypeptide and suppression of protein aggregation under stress conditions. A prokaryotic Hsp70 protein, DnaK, cooperatively works with DnaJ (Hsp40) and GrpE, and these three proteins constitute the DnaK chaperone system (Figure 1). DnaJ is a molecular chaperone as well as DnaK and interacts with polypeptide chains prior to DnaK. DnaJ facilitates the ATPase activity of DnaK, by which high affinity property of DnaK for substrates is brought about. GrpE promotes ADP-ATP nucleotide exchange of DnaK and substrate release from DnaK. When exposed to heat shock conditions, GrpE is temporarily unable to interact with DnaK, resulting in arrest of the DnaK chaperone cycle and substrate holding by DnaK. Reversible conformational changes in GrpE at heat shock conditions are responsible for this thermosensing function, which is significant process for prevention of protein thermal denaturation.
GrpE is a homodimeric protein and consists of the N-terminal α-helix domain, central four-helix bundle domain, and C-terminal β-sheet domain. It is suggested that an ADP molecule bound to the nucleotide binding domain (NBD) of DnaK is removed by insertion of the β-sheet domain of GrpE into NBD of DnaK. Biochemical experiments conducted by authors indicate that partial unfolding of the DnaK interaction region (mainly consist of the β-sheet domain) of T. thermophilus GrpE under heat shock conditions (at 90°C) is the structural basis for its thermosensing function.
Protein Data Bank (PDB)
author: Akira Nakamura