Interleukin-8-like activity in a filarial asparaginyl-tRNA synthetase.
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.
Department of Medicine, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, WI 53092, USA. mkron@mcw.edu
Michael A
MA
Kron
Cheng
C
Wang
Sanja
S
Vodanovic-Jankovic
O M Zack
OM
Howard
Leslie A
LA
Kuhn
D000595:Amino Acid Sequence; D000818:Animals; D001226:Aspartate-tRNA Ligase / Q000276:immunology*; D017178:Brugia malayi / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D002633:Chemotaxis; D019295:Computational Biology / Q000379:methods; D004789:Enzyme Activation; D015801:Helminth Proteins / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology; D017434:Protein Structure, Tertiary; D012346:RNA, Transfer, Amino Acyl / Q000276:immunology*; D053700:Receptors, Interleukin-8 / Q000276:immunology; D017386:Sequence Homology, Amino Acid
D015801:Helminth Proteins; D007155:Immunologic Factors; D016209:Interleukin-8; D012346:RNA, Transfer, Amino Acyl; D053700:Receptors, Interleukin-8; D001226:Aspartate-tRNA Ligase; C029194:asparaginyl-tRNA synthetase