Semisynthesis of an evasin from tick saliva reveals a critical role of tyrosine sulfation for chemokine binding and inhibition

Charlotte Franck, Simon R. Foster, Jason Johansen-Leete, Sayeeda Chowdhury, Michelle Cielesh, Ram Prasad Bhusal, Joel P. Mackay, Mark Larance, Martin J. Stone, Richard J. Payne

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Blood-feeding arthropods produce antiinflammatory salivary proteins called evasins that function through inhibition of chemokine-receptor signaling in the host. Herein, we show that the evasin ACA-01 from the Amblyomma cajennense tick can be posttranslationally sulfated at two tyrosine residues, albeit as a mixture of sulfated variants. Homogenously sulfated variants of the proteins were efficiently assembled via a semisynthetic native chemical ligation strategy. Sulfation significantly improved the binding affinity of ACA-01 for a range of proinflammatory chemokines and enhanced the ability of ACA-01 to inhibit chemokine signaling through cognate receptors. Comparisons of evasin sequences and structural data suggest that tyrosine sulfation serves as a receptor mimetic strategy for recognizing and suppressing the proinflammatory activity of a wide variety of mammalian chemokines. As such, the incorporation of this posttranslational modification (PTM) or mimics thereof into evasins may provide a strategy to optimize tick salivary proteins for antiinflammatory applications.

Original languageEnglish
Pages (from-to)12657-12664
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number23
DOIs
Publication statusPublished - 9 Jun 2020

Keywords

  • Antiinflammatory
  • Chemokines
  • Evasins
  • Sulfation
  • Ticks

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