Chaperone DnaJ
Encyclopedia
In molecular biology, chaperone DnaJ, also known as Hsp40 (heat shock protein 40 kD), is a molecular chaperone protein. It is expressed in a wide variety of organisms from bacteria to humans.
is an enzyme that couples cycles of ATP
binding, hydrolysis, and ADP
release by an N-terminal ATP-hydrolizing 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. 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 acid
consensus sequence known as the J domain. The J domain of DnaJ interacts with Hsp70
heat shock proteins. DnaJ heat-shock proteins play a role in regulating the ATPase
activity of Hsp70 heat-shock proteins.
Besides stimulating the ATPase activity of DnaK through its J-domain, DnaJ also associates with unfolded polypeptide chains and prevents their aggregation. 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.
-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. A C-terminal domain, the function of which is unknown.
; DNAJA2
; DNAJA3
; DNAJA4; DNAJB1
; DNAJB11
; DNAJB13; DNAJB4
;
DNAJB5; MST104;
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 DnaKHsp70
The 70 kilodalton heat shock proteins are a family of ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms...
is an enzyme that couples cycles of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
binding, hydrolysis, and ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
release by an N-terminal ATP-hydrolizing 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. DnaK is itself a weak ATPase
ATPase
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...
; 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 acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
consensus sequence known as the J domain. The J domain of DnaJ interacts with Hsp70
Hsp70
The 70 kilodalton heat shock proteins are a family of ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms...
heat shock proteins. DnaJ heat-shock proteins play a role in regulating the ATPase
ATPase
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...
activity of Hsp70 heat-shock proteins.
Besides stimulating the ATPase activity of DnaK through its J-domain, DnaJ also associates with unfolded polypeptide chains and prevents their aggregation. 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 J domain (described above). A central cysteineCysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
-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. A C-terminal domain, the function of which is unknown.
Human proteins containing a DnaJ domain
DNAJA1DNAJA1
DnaJ homolog subfamily A member 1 is a protein that in humans is encoded by the DNAJA1 gene.-Further reading:...
; DNAJA2
DNAJA2
DnaJ homolog subfamily A member 2 is a protein that in humans is encoded by the DNAJA2 gene.-Further reading:...
; DNAJA3
DNAJA3
DnaJ homolog subfamily A member 3, mitochondrial is a protein that in humans is encoded by the DNAJA3 gene.-Interactions:DNAJA3 has been shown to interact with HSPA8, RAS p21 protein activator 1 and Janus kinase 2.-Further reading:...
; DNAJA4; DNAJB1
DNAJB1
DnaJ homolog subfamily B member 1 is a protein that in humans is encoded by the DNAJB1 gene.-Interactions:DNAJB1 has been shown to interact with STUB1 and HSPA4.-Further reading:...
; DNAJB11
DNAJB11
DnaJ homolog subfamily B member 11 is a protein that in humans is encoded by the DNAJB11 gene.-Further reading:...
; DNAJB13; DNAJB4
DNAJB4
DnaJ homolog subfamily B member 4 is a protein that in humans is encoded by the DNAJB4 gene.-Further reading:...
;
DNAJB5; MST104;