QKRAA氨基酸基序的功能：介导DnaJ与DnaK的结合。对类风湿性关节炎与HLA - DR4关联的启示。
A function for the QKRAA amino acid motif: mediating binding of DnaJ to DnaK. Implications for the association of rheumatoid arthritis with HLA-DR4.
作者信息
Auger I, Roudier J
机构信息
Laboratoire d'Immuno Rhumatologie, Faculté de Médecine de Marseille, France.
出版信息
J Clin Invest. 1997 Apr 15;99(8):1818-22. doi: 10.1172/JCI119348.
Abstract
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.
摘要
氨基酸基序QKRAA在HLA - DRB1上表达时，会增加患类风湿性关节炎的易感性。该基序是强大的B细胞和T细胞表位的基础。此外，它在蛋白质数据库中高度富集，表明它具有自身的功能。为了确定该功能，我们使用QKRAA肽亲和柱筛选大肠杆菌的总蛋白提取物。我们发现，大肠杆菌70-kD热休克蛋白DnaK能结合QKRAA。有趣的是，DnaK有一个天然配体DnaJ，其含有QKRAA基序。我们发现含QKRAA的肽会抑制DnaK与DnaJ的结合。此外，针对QKRAA基序的兔抗体可抑制DnaJ与DnaK的结合。这些数据表明，QKRAA介导大肠杆菌伴侣蛋白DnaJ与其伴侣蛋白DnaK的结合。
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