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- Title
Crystal Structure of an EMAP-II-Like Cytokine Released from a Human tRNA Synthetase.
- Authors
Xiang-Lei Yang; Jianming Liu; Robert J. Skene; Duncan E. McRee; Paul Schimmel
- Abstract
Aminoacyl-tRNA synthetases catalyze the first step of protein synthesis by aminoacylation of tRNAs. Remarkably, biological fragments of two human enzymes tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase are active cytokines produced by proteolysis or alternative splicing. One is a C-terminal fragment of TyrRS (C-TyrRS) that has potent activity for chemotaxis of leukocytes and monocytes and for stimulating production of other cytokines. Significantly, the cytokine activity of C-TyrRS is absent in the context of the full-length native protein. Unknown is the mechanism by which domain-release from the dimeric native protein activates the cytokine. Here, the crystal structure of C-TyrRS is presented at 2.2 Å resolution. This structure is similar to that of endothelial monocyte-activating protein II (EMAP-II), with critical residues of a heptapeptide element important for chemotaxis activity exposed on the first strand of a β-barrel of the monomeric unit. In contrast, the same residues of C-TyrRS are buried in an operational model for native TyrRS. Importantly, C-TyrRS is shown here to be monomeric when released from dimeric native TyrRS. Further analysis suggests that the critical residues are exposed when tRNA is bound. Thus, tRNA binding to native TyrRS may be an additional or alternative way to activate cytokine signaling.
- Subjects
CHEMICAL structure; MOLECULAR structure; TRANSFER RNA; PROTEIN synthesis
- Publication
Helvetica Chimica Acta, 2003, Vol 86, Issue 4, p1246
- ISSN
0018-019X
- Publication type
Article