Poster Presentation The 43rd Lorne Conference on Protein Structure and Function 2018

Chemokine-Inhibiting Evasin Proteins Are Encoded Within Diverse Genera of Ticks (#114)

Sayeeda Chowdhury 1 , Martin Stone 1 , Jenni Hayward 1 , Meritxell Canals 2 , Richard Payne 3 , Julie Sanchez 2 , Cheng Huang 1
  1. Monash University, Clayton, VIC, Australia
  2. Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Melbourne, Vic, Australia
  3. Organic Chemistry and Chemical Biology, The University of Sydney, Sydney, NSW, Australia

Ticks secrete many salivary factors, which target host defence molecules and allow them to prolong their residence time on their hosts. Specifically, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins known as ‘evasins’, which bind to host chemokines, thus inhibiting the recruitment of leukocytes to the location of the tick bite. Evasins could have valuable anti-inflammatory therapeutic potential. Using sequence similarity searches, our lab has identified 257 new putative evasin sequences encoded by the genomes of numerous hard tick species, spanning the genera Rhipicephalus, Amblyomma and Ixodes of the Ixodidae family. Nine representative sequences were successfully expressed in E. coli and eight of the nine candidates exhibited high affinity binding to human chemokines. Sequence alignments enabled classification of the evasins into several subfamilies based on the number of conserved cysteine residues: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), with the previously characterised evasin-1 and evasin-4 from R. sanguineus. C6 evasins have only three of these disulfide bonds and are prevalent in ticks from the genus Ixodes. C10 and C12 evasins appear to each contain two evasin-like domains, giving them the possibility of binding simultaneously to two chemokine molecules. Most of the identified sequences from all of these subfamilies possess putative tyrosine sulfation sites, a feature also found in a chemokine-binding region of chemokine receptors. We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defences, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.