A function for the QKRAA amino acid motif: mediating binding of DnaJ to DnaK. Implications for the association of rheumatoid arthritis with HLA-DR4.
The amino acid motif QKRAA, when expressed on HLA-DRB1, carries susceptibility to develop rheumatoid arthritis. This motif is the basis of strong B and T cell epitopes. Furthermore, it is highly overrepresented in protein databases, suggesting that it carries a function of its own. To identify this function, we used QKRAA peptide affinity columns to screen total protein extracts from Escherichia coli. We found that DnaK, the E. coli 70-kD heat shock protein, binds QKRAA. Of interest, DnaK has a natural ligand, DnaJ, that contains a QKRAA motif. We found that QKRAA-containing peptides inhibit the binding of DnaK to DnaJ. Furthermore, rabbit antibody to the QKRAA motif can inhibit binding of DnaJ to DnaK. These data suggest that QKRAA mediates the binding of E. coli chaperone DnaJ to its partner chaperone DnaK.
Auger
I
I
Laboratoire d'Immuno Rhumatologie, Faculté de Médecine de Marseille, France.
Roudier
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D011485:Protein Binding; D011817:Rabbits; D017386:Sequence Homology, Amino Acid
D000906:Antibodies; D001426:Bacterial Proteins; C494635:DnaJ protein, E coli; D029968:Escherichia coli Proteins; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008024:Ligands; C063842:dnaK protein, E coli