A novel anti-tumor cytokine contains an RNA binding motif present in aminoacyl-tRNA synthetases.
Endothelial monocyte-activating polypeptide II (EMAP II) is a novel pro-apoptotic cytokine that shares sequence homology with the C-terminal regions of several tRNA synthetases. Pro-EMAP II, the precursor of EMAP II, is associated with the multi-tRNA synthetase complex and facilitates aminoacylation activity. The structure of human EMAP II, solved at 1.8 A resolution, revealed the oligomer-binding fold for binding different tRNAs and a domain that is structurally homologous to other chemokines. The similar structures to the RNA binding motif of EMAP II was previously observed in the anticodon binding domain of yeast Asp-tRNA synthetase (AspRSSC) and the B2 domain of Thermus thermophilus Phe-tRNA synthetase. The RNA binding pattern of EMAP II is likely to be nonspecific, in contrast to the AspRSSC. The peptide sequence that is responsible for cytokine activity is located, for the most part, in the beta1 strand. It is divided into two regions by a neighboring loop.
Kim
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School of Chemical Engineering, Yeungnam University, 214-1 Dae-Dong, Kyungsan Kyungbuk 712-749, South Korea. ykim1@u.washington.edu
Shin
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Li
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Cheong
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Kim
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Kim
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D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D016207:Cytokines; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D000970:Antineoplastic Agents; D016207:Cytokines; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1; D012313:RNA; D000604:Amino Acyl-tRNA Synthetases