Interaction of murine BiP/GRP78 with the DnaJ homologue MTJ1

The activity of Hsp70 proteins is regulated by accessory proteins, among wh ich the most studied are the members of the DnaJ-like protein family. BiP/G RP78 chaperones the translocation and maturation of secreted and membrane p roteins in the endoplasmic reticulum. No DnaJ-like partner has been describ ed so far to regulate the function of mammalian BiP/GRP78. We show here tha t murine BiP/GRP78 interacts with the lumenal J domain of the murine transm embrane protein MTJ1 (J-MTJ1). J-MTJ1 stimulates the ATPase activity of BiP /GRP78 at stoichiometric concentrations. The C-terminal tail of BiP/GRP78 i s not required for the interaction with J-MTJ1, leaving the function of thi s portion of the molecule still unclear. Physical interactions between J-MT J1 and BiP/GRP78 are stable and can be abolished by a single histidine --> glutamine substitution in the highly conserved HPD motif shared by all DnaJ -like proteins. The J-MTJ1 fragment, but not the mutant J-MTJ1:H89Q fragmen t, stimulates the ATPase activity of Escherichia coli DnaK, although at a h igher concentration than its genuine partner DnaJ. Full-length DnaJ does no t stimulate BiP over the range of concentrations investigated. These result s indicate that the J domain of MTJ1 is sufficient for its interaction with BiP/GRP78 and cannot be substituted by E. coli DnaJ.