Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 23, Pages 12657-12664Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2000605117
Keywords
chemokines; sulfation; ticks; evasins; antiinflammatory
Categories
Funding
- Australian Research Council Discovery Project [DP190101526]
- National Health and Medical Research Council [APP1140867, APP1174941]
- John A. Lamberton Research Scholarship
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Blood-feeding arthropods produce antiinflammatory salivary pro-teins 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 posttransla-tionally 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 af-finity 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 re-ceptor mimetic strategy for recognizing and suppressing the proin-flammatory 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.
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