PROSITE documentation PDOC00553

J-protein family domains signature and profiles




Description

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):

  • Yeast protein MAS5/YDJ1 that is involved in protein folding and mitochondrial protein import.
  • Yeast protein MDJ1 that is involved in protein folding and mitochondrial protein import.
  • Yeast protein SCJ1 that is involved in protein folding in the lumen of the endoplasmic reticulum.
  • Yeast protein APJ1/YNL077w, that might modulate folding reaction.
  • Cucumber dnaJ homolog anchored at the glyoxysomal membrane.
  • Yeast protein XDJ1.
  • Human protein HDJ2.

The type 2 contains proteins with a J-domain, a G/F domain and a CTD domain:

  • Rhizobium fredii nolC, a protein involved in cultivar-specific nodulation of soybean.
  • Escherichia coli cbpA, a protein that binds curved DNA.
  • Yeast protein SIS1, required for nuclear migration during mitosis.
  • Yeast protein CAJ1.
  • Yeast hypothetical protein YFR041c.
  • Yeast hypothetical protein YIR004w.
  • Yeast hypothetical protein YJL162c.
  • Plasmodium falciparum ring-infected erythrocyte surface antigen (RESA). RESA, whose function is not known, is associated with the membrane skeleton of newly invaded erythrocytes.
  • Human HDJ1.
  • Human HSJ1, a neuronal protein.
  • Drosophila cysteine-string protein (csp).

The type 3 subgroup contains proteins that have only the J-domain:

  • Yeast protein SEC63/NPL1. It is important for protein assembly into the endoplasmic reticulum and the nucleus.
  • Eukaryotic Tim14 protein. An essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. In the complex, it is required to stimulate activity of mtHSP70 (SSC1).
  • Yeast Jac1 protein and HscB eukaryotic homologues. They may act as co-chaperones in iron-sulfur cluster assembly in mitochondria.
  • Yeast Zuo1 protein. Zuo1 and Ssz1 (hsp70) are targeted to ribosomes, where they form the functionally active RAC complex.
  • Yeast Jjj1 to 3, Erj5 and Jid1 proteins of unknown function.

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:

Kelley W.

Last update:

April 2006 / Text revised; profiles added; pattern deleted.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

DNAJ_2, PS50076; dnaJ domain profile  (MATRIX)

ZF_CR, PS51188; Zinc finger CR-type profile  (MATRIX)

DNAJ_1, PS00636; Nt-dnaJ domain signature  (PATTERN)


References

1AuthorsFrydman J.
TitleFolding of newly translated proteins in vivo: the role of molecular chaperones. Pubmed=11395418
SourceAnnu. Rev. Biochem. 70:603-647(2001).

2AuthorsWalsh P., Bursac D., Law Y.C., Cyr D., Lithgow T.;
TitleThe J-protein family: modulating protein assembly, disassembly and translocation.
SourceEMBO Rep. 5:567-571(2004).

3AuthorsPellecchia M., Szyperski T., Wall D., Georgopoulos C., Wuthrich K.
TitleNMR structure of the J-domain and the Gly/Phe-rich region of the Escherichia coli DnaJ chaperone.
SourceJ. Mol. Biol. 260:236-250(1996).
PubMed ID8764403
DOI10.1006/jmbi.1996.0395

4AuthorsMartinez-Yamout M., Legge G.B., Zhang O., Wright P.E., Dyson H.J.
TitleSolution structure of the cysteine-rich domain of the Escherichia coli chaperone protein DnaJ.
SourceJ. Mol. Biol. 300:805-818(2000).
PubMed ID10891270

5AuthorsGenevaux P., Schwager F., Georgopoulos C., Kelley W.L.
TitleScanning mutagenesis identifies amino acid residues essential for the in vivo activity of the Escherichia coli DnaJ (Hsp40) J-domain.
SourceGenetics 162:1045-1053(2002).
PubMed ID12454054

6AuthorsLinke K., Wolfram T., Bussemer J., Jakob U.
TitleThe roles of the two zinc binding sites in DnaJ.
SourceJ. Biol. Chem. 278:44457-44466(2003).
PubMed ID12941935



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