In molecular biology, chaperone DnaJ, also known as Hsp40 (
heat shock protein 40 kDa), is a molecular
chaperone protein. It is expressed in a wide variety of organisms from bacteria to humans.[1][2]
Function
Molecular chaperones are a diverse family of proteins that function to protect proteins from irreversible
aggregation during synthesis and in times of
cellular stress. The bacterial molecular chaperone
DnaK is an enzyme that couples cycles of
ATP binding,
hydrolysis, and
ADP release by an N-terminal ATP-hydrolyzing domain to cycles of sequestration and release of unfolded proteins by a
C-terminal substrate binding domain. Dimeric
GrpE is the
co-chaperone for DnaK, and acts as a
nucleotide exchange factor, stimulating the rate of ADP release 5000-fold.[3] DnaK is itself a weak
ATPase;
ATP hydrolysis by DnaK is stimulated by its interaction with another co-chaperone, DnaJ. Thus the co-chaperones DnaJ and GrpE are capable of tightly regulating the nucleotide-bound and substrate-bound state of DnaK in ways that are necessary for the normal
housekeeping functions and stress-related functions of the DnaK molecular chaperone cycle.
This family of proteins contain a 70
amino acidconsensus sequence known as the J domain. The J domain of DnaJ interacts with
Hsp70 heat shock proteins.[4] DnaJ heat-shock proteins play a role in regulating the
ATPase activity of Hsp70 heat-shock proteins.[5][6]
Besides stimulating the ATPase activity of DnaK through its J-domain, DnaJ also associates with unfolded polypeptide chains and prevents their aggregation.[7] Thus, DnaK and DnaJ may bind to one and the same polypeptide chain to form a
ternary complex. The formation of a ternary complex may result in cis-interaction of the J-domain of DnaJ with the ATPase domain of DnaK. An unfolded polypeptide may enter the chaperone cycle by associating first either with ATP-liganded DnaK or with DnaJ. DnaK interacts with both the
backbone and
side chains of a peptide substrate; it thus shows binding polarity and admits only L-peptide segments. In contrast, DnaJ has been shown to bind both L- and D-peptides and is assumed to interact only with the side chains of the substrate.
Domain architecture
Proteins in this family consist of three
domains. The
N-terminal domain is the J domain (described above). The central domain is a
cysteine-rich region, which contains four repeats of the motif CXXCXGXG where X is any amino acid. The isolated cysteine rich domain folds in
zinc dependent fashion. Each set of two repeats binds one unit of zinc. Although this domain has been implicated in substrate binding, no evidence of specific interaction between the isolated DNAJ cysteine rich domain and various hydrophobic peptides has been found. This domain has
disulphide isomerase activity.[8] The function of the C-terminal is chaperone and dimerization.
^Qiu XB, Shao YM, Miao S, Wang L (November 2006). "The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones". Cellular and Molecular Life Sciences. 63 (22): 2560–70.
doi:
10.1007/s00018-006-6192-6.
PMID16952052.
S2CID21325339.
^Martinez-Yamout, M.; Legge, G. B.; Zhang, O.; Wright, P. E.;
Dyson, H. J. (2000). "Solution Structure of the Cysteine-rich Domain of the Escherichia coli Chaperone Protein DnaJ☆☆☆". Journal of Molecular Biology. 300 (4): 805–818.
doi:
10.1006/jmbi.2000.3923.
PMID10891270.