Interleukin-8-like activity in a filarial asparaginyl-tRNA synthetase

• Published in: Molecular and biochemical parasitology 2012-09, Vol.185 (1), p.66-69
• Main Authors: Kron, Michael A., Wang, Cheng, Vodanovic-Jankovic, Sanja, Zack Howard, O.M., Kuhn, Leslie A.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; amino acids; aminoacyl tRNA ligases; Aminoacyl-tRNA synthetase; Animals; Aspartate-tRNA Ligase - immunology; Brugia malayi; Brugia malayi - enzymology; Brugia malayi - genetics; Brugia malayi - immunology; cell growth; Chemokine; Chemotaxis; Computational Biology - methods; Enzyme Activation; Filaria; Helminth Proteins - immunology; Humans; Immunologic Factors - immunology; Immunoregulation; interleukin-8; Interleukin-8 (IL-8); Interleukin-8 - immunology; mitochondrial RNA; Molecular Sequence Data; Neutrophils - immunology; parasitology; Protein Structure, Tertiary; Receptors; Receptors, Interleukin-8 - immunology; RNA splicing; RNA, Transfer, Amino Acyl - immunology; Sequence Homology, Amino Acid; transcription (genetics)
• ISSN: 0166-6851; 1872-9428
• DOI: 10.1016/j.molbiopara.2012.06.003

[Display omitted] Brugia malayi AsnRS has IL-8 like activity. ► IL-8-like activity resides in the tRNA binding domain of the filarial AsnRS. ► Structural homology exists with regions key to receptor binding by human IL-8. A wide range of secondary biological functions have been documented for eukaryotic aminoacyl-tRNA synthetases including roles in transcriptional regulation, mitochondrial RNA splicing, cell growth, and chemokine-like activities. The asparaginyl-tRNA synthetase (AsnRS) of the filarial nematode, Brugia malayi, is a highly expressed excretory–secretory molecule which activates interleukin 8 (IL-8) receptors via extracellular domains that are different from those used by IL-8. Recent success in determining the complete atomic structure of the B. malayi AsnRS provided the opportunity to map its chemokine-like activity. Chemotaxis assays demonstrated that IL-8-like activity is localized in a novel 80 amino acid amino terminal substructure. Structural homology searches revealed similarities between that domain in B. malayi AsnRS and substructures involved in receptor binding by human IL-8. These observations provide important new insights into how parasite-derived molecules may play a role in the modulation of immune cell function.