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Human anti‐asparaginyl‐tRNA synthetase autoantibodies (anti‐KS) increase the affinity of the enzyme for its tRNA substrate
Author(s) -
Beaulande Mélanie,
Kron Michael,
Härtlein Michael
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02340-7
Subject(s) - epitope , autoantibody , aminoacylation , biochemistry , aminoacyl trna synthetase , transfer rna , enzyme , biology , amino acid , microbiology and biotechnology , antibody , chemistry , rna , immunology , gene
Autoantibodies directed against specific human aminoacyl‐tRNA synthetases have been associated with a clinical picture including myositis, arthritis, interstitial lung disease and other features that has been referred to as the ‘anti‐synthetase syndrome’. Anti‐asparaginyl‐tRNA synthetase autoantibodies (anti‐KS), the most recently described anti‐synthetase autoantibodies, are directed against human cytosolic asparaginyl‐tRNA synthetase and neutralize specifically its activity. Here we show that these antibodies recognize two epitopes on the human enzyme, an N‐terminal epitope reactive in immunoblot experiments and a heat‐labile epitope in the catalytic domain. In contrast to the well studied anti‐Jo‐1 autoantibodies anti‐KS when bound to the synthetase increase the affinity of the synthetase for its tRNA substrate and prevent aminoacylation without interfering with the amino acid activation step.