|PROSITE documentation PDOC00553 [for PROSITE entry PS50076]|
The hsp70 chaperone machine (see <PDOC00269>) performs many diverse roles in the cell, including folding of nascent proteins, translocation of polypeptides across organelle membranes, coordinating responses to stress, and targeting selected proteins for degradation. DnaJ is a member of the hsp40 family of molecular chaperones, which is also called the J-protein family, the members of which regulate the activity of hsp70s. DnaJ (hsp40) binds to dnaK (hsp70) and stimulates its ATPase activity, generating the ADP-bound state of dnaK, which interacts stably with the polypeptide substrate [1,2].
DnaJ consists of an N-terminal conserved domain (called 'J' domain) of about 70 amino acid residues, a glycine and phenylalanine-rich domain ('G/F' domain), a central cysteine rich domain (CR-type zinc finger) containing four repeats of a CXXCXGXG motif which can coordinate two zinc atom and a C-terminal domain (CTD) .
Such a structure is shown in the following schematic representation:
+------------+-+-----------+-----+-----------+-------------+ | J-domain | | Gly/Phe-R | | CXXCXGXG | CTD | +------------+-+-----------+-----+-----------+-------------+
The structures of the 'J' domain (see <PDB:1XBL>) and the 'CR' domain (see <PDB:1EXK>) have been solved [3,4]. The J domain consists of four helices, the second of which has a charged surface that includes basic residues that are essential for interaction with the ATPase domain of hsp70 . The CR-type zinc finger has an overall V-shaped extended β-hairpin topology and two symmetrical zinc binding sites, designated as Zn1 and Zn2: Zn1 is formed by the two cysteine motifs that are furthest apart in the primary sequence, while Zn2 is formed by the two central, adjacent cysteine motifs . It has been shown that Zn1 is important for the autonomous, dnaK-independent chaperone activity, while Zn2 is a necessary interaction site with dnaK, which seems to be crucial for in vivo function in the dnaJ/dnaK system .
J-protein family are classified in three classes :
The type 1 contains proteins with a J-domain, a G/F domain, a CR zinc finger and a CTD domain (true homologues of dnaJ):
The type 2 contains proteins with a J-domain, a G/F domain and a CTD domain:
The type 3 subgroup contains proteins that have only the J-domain:
We developed a signature pattern for the 'J' domain, based on conserved positions in the C-terminal half of this domain. We also developed two profiles, one which covers the entire 'J' domain and the other that spans the whole CR-type zinc finger.Expert(s) to contact by email:
April 2006 / Text revised; profiles added; pattern deleted.
PROSITE methods (with tools and information) covered by this documentation:
|Title||Folding of newly translated proteins in vivo: the role of molecular chaperones. Pubmed=11395418|
|Source||Annu. Rev. Biochem. 70:603-647(2001).|
|2||Authors||Walsh P., Bursac D., Law Y.C., Cyr D., Lithgow T.;|
|Title||The J-protein family: modulating protein assembly, disassembly and translocation.|
|Source||EMBO Rep. 5:567-571(2004).|
|3||Authors||Pellecchia M., Szyperski T., Wall D., Georgopoulos C., Wuthrich K.|
|Title||NMR structure of the J-domain and the Gly/Phe-rich region of the Escherichia coli DnaJ chaperone.|
|Source||J. Mol. Biol. 260:236-250(1996).|
|4||Authors||Martinez-Yamout M., Legge G.B., Zhang O., Wright P.E., Dyson H.J.|
|Title||Solution structure of the cysteine-rich domain of the Escherichia coli chaperone protein DnaJ.|
|Source||J. Mol. Biol. 300:805-818(2000).|
|5||Authors||Genevaux P., Schwager F., Georgopoulos C., Kelley W.L.|
|Title||Scanning mutagenesis identifies amino acid residues essential for the in vivo activity of the Escherichia coli DnaJ (Hsp40) J-domain.|
|6||Authors||Linke K., Wolfram T., Bussemer J., Jakob U.|
|Title||The roles of the two zinc binding sites in DnaJ.|
|Source||J. Biol. Chem. 278:44457-44466(2003).|