InterPro: IPR018253 Heat shock protein DnaJ, conserved site

The hsp70 chaperone machine 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.

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:

  +------------+-+-------+-----+-----------+--------------------------------+
  | N-terminal | | Gly-R |     | CXXCXGXG  | C-terminal                     |
  +------------+-+-------+-----+-----------+--------------------------------+

The structures of the 'J' domain and the 'CR' domain have been solved [1, 2]. 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 [3]. The CR-type zinc finger has an overall V-shaped extended beta-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 [2]. 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 [4].