In molecular biology, chaperone DnaJ, also known as Hsp40 (
heat shock protein
Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including expo ...
40 kD), is a molecular
chaperone protein
In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assi ...
. It is expressed in a wide variety of organisms from bacteria to humans.
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
ATP may refer to:
Companies and organizations
* Association of Tennis Professionals, men's professional tennis governing body
* American Technical Publishers, employee-owned publishing company
* ', a Danish pension
* Armenia Tree Project, non ...
binding, hydrolysis, and
ADP
Adp or ADP may refer to:
Aviation
* Aéroports de Paris, airport authority for the Parisian region in France
* Aeropuertos del Perú, airport operator for airports in northern Peru
* SLAF Anuradhapura, an airport in Sri Lanka
* Ampara Air ...
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 GrpE (''Gro-P'' like protein E) is a bacterial nucleotide exchange factor that is important for regulation of protein folding machinery, as well as the heat shock response. It is a heat-inducible protein and during stress it prevents unfolded prote ...
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
ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...
; 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 acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
consensus sequence known as the J domain. The J domain of DnaJ interacts with
Hsp70
The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an importa ...
heat shock proteins.
DnaJ heat-shock proteins play a role in regulating the
ATPase
ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...
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
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
domain is the J domain (described above). The central domain is a
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, sometime ...
-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.
The function of the C-terminal is chaperone and dimerization.
Proteins containing a DnaJ domain
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Homo sapiens
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
'':
DNAJA1
DnaJ homolog subfamily A member 1 is a protein that in humans is encoded by the ''DNAJA1'' gene.
Interactions
DNAJA1 has been shown to interact with PTTG1
Securin is a protein that in humans is encoded by the ''PTTG1'' gene.
Function
The en ...
;
DNAJA2
DnaJ homolog subfamily A member 2 is a protein that in humans is encoded by the ''DNAJA2'' gene.
The protein encoded by this gene shares sequence similarity with Hir1p and Hir2p, the two corepressors of histone gene transcription characterized in ...
;
DNAJA3
DnaJ homolog subfamily A member 3, mitochondrial, also known as Tumorous imaginal disc 1 (TID1), is a protein that in humans is encoded by the ''DNAJA3'' gene on chromosome 16. This protein belongs to the DNAJ/Hsp40 protein family, which is known ...
;
DNAJA4
DnaJ heat shock protein family (Hsp40) member A4 is a protein that in humans is encoded by the DNAJA4 gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." mean ...
(MST104);
DNAJB1;
DNAJB11
DnaJ homolog subfamily B member 11 is a protein that in humans is encoded by the ''DNAJB11'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''gen ...
;
DNAJB13;
DNAJB4
DnaJ homolog subfamily B member 4 is a protein that in humans is encoded by the ''DNAJB4'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''gener ...
;
DNAJB5;
DNAJB6;
DNAJC17;
DNAJC28
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Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
'':
ZUO1
References
{{DEFAULTSORT:Chaperone Dnaj
Protein domains
Protein families
Co-chaperones