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PROSITE documentation PDOC00553 |
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) [2].
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 [5]. 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 [4]. 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 [6].
J-protein family are classified in three classes [2]:
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: Last update:April 2006 / Text revised; profiles added; pattern deleted.
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PROSITE methods (with tools and information) covered by this documentation:
1 | Authors | Frydman J. |
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). | |
PubMed ID | 8764403 | |
DOI | 10.1006/jmbi.1996.0395 |
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). | |
PubMed ID | 10891270 |
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. | |
Source | Genetics 162:1045-1053(2002). | |
PubMed ID | 12454054 |
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). | |
PubMed ID | 12941935 |