Tandem Domain Evasins: Inhibitors of Chemokine-mediated Inflammation — ASN Events
  1. Schedule
  2. Poster Session 1 and Drinks
  3. Tandem Domain Evasins: Inhibitors of Chemokine-mediated Inflammation

Tandem Domain Evasins: Inhibitors of Chemokine-mediated Inflammation (#114)

Ram P Bhusal 1 , Jenni Hayward 1 , Pramod Aryal 1 , Shankar R Devkota 1 , Sayeeda Chowdhury 1 , Andrew Perry 2 , Martin J Stone 1
  1. Infection and Immunity Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia
  2. Monash Bioinformatics Platform, Monash University, Clayton, VIC 3800, Australia

Inflammation is the complex physiological response to tissue injury or infection. Leukocyte recruitment is an important feature of inflammation. Leukocyte recruitment is regulated by small proteins called chemokines, which are secreted at the site of injury or infection, binding to chemokine receptors expressed on the target leukocyte. As an evolutionary strategy, ticks have been found to secrete small chemokine binding proteins (CBPs) called evasins, which suppress the host inflammatory response, enabling the tick to avoid detection and prolong blood feeding (1). Inhibition of specific chemokines is crucial for preventing inflammation. As such, evasins are natural, selective chemokine-inhibitory proteins with excellent potential as therapeutics for inflammatory diseases. In recent years, we and others have discovered a large family of tick evasins that bind and inhibit chemokines (2,3). In this study, we have used bioinformatics methods to discover a novel family of these CBPs that contain tandem repeats of evasin-like sequences. Furthermore, we have combined the use of molecular biology, protein chemistry and biophysical methods to verify and characterise the binding of tandem domain evasins to chemokines. Our work may pave the way for the development of new therapeutic agents against inflammation.

  1. Frauenschuh, A., Power, C. A., Déruaz, M., Ferreira, B. R., Silva, J. S., Teixeira, M. M., Dias, J. M., Martin, T., Wells, T. N., and Proudfoot, A. E. (2007) Molecular cloning and characterization of a highly selective chemokine-binding protein from the tick Rhipicephalus sanguineus. Journal of Biological Chemistry 282, 27250-27258
  2. Hayward, J., Sanchez, J., Perry, A., Huang, C., Valle, M. R., Canals, M., Payne, R. J., and Stone, M. J. (2017) Ticks from diverse genera encode chemokine-inhibitory evasin proteins. Journal of Biological Chemistry 292, 15670–15680
  3. Singh, K., Davies, G., Alenazi, Y., Eaton, J. R., Kawamura, A., and Bhattacharya, S. (2017) Yeast surface display identifies a family of evasins from ticks with novel polyvalent CC chemokine-binding activities. Scientific reports 7, 4267