Sulfation of the Human Cytomegalovirus Protein UL22A Enhances Binding to the Chemokine RANTES

Wang, Xiaoyi; Stone, Martin J.

doi:10.1002/ange.201703059

Cited by 12 publications

(8 citation statements)

References 42 publications

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“…and -4 contain tyrosine residues adjacent to several acidic residues (sequences EDDEDY and EEEDDY, respectively), which we identified as likely to be post-translationally sulfated (12,31,32). This feature of evasin sequences has not been identified previously.…”

Section: Tick Evasins From Diverse Generasupporting

confidence: 46%

Ticks from diverse genera encode chemokine-inhibitory evasin proteins

Hayward

Sanchez

Perry

et al. 2017

Journal of Biological Chemistry

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To prolong residence on their hosts, ticks secrete many salivary factors that target host defense molecules. In particular, the tick has been shown to produce three salivary glycoproteins named "evasins," which bind to host chemokines, thereby inhibiting the recruitment of leukocytes to the location of the tick bite. Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera, , and of the Ixodidae family. Nine representative sequences were successfully expressed in , and eight of the nine candidates exhibited high-affinity binding to human chemokines. Sequence alignments enabled classification of the evasins into two subfamilies: C evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C evasins have only three of these disulfide bonds. Most of the identified sequences contain predicted secretion leader sequences, -linked glycosylation sites, and a putative site of tyrosine sulfation. 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 defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.

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Section: Tick Evasins From Diverse Generasupporting

confidence: 46%

Ticks from diverse genera encode chemokine-inhibitory evasin proteins

Hayward

Sanchez

Perry

et al. 2017

Journal of Biological Chemistry

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“…These include CCR2 ligands CCL2 (monocyte chemoattractant protein-1, MCP-1), CCL7 (MCP-3), and CCL8 (MCP-2) and CCR3 ligands CCL11 (eotaxin-1), CCL24 (eotaxin-2), and CCL26 (eotaxin-3) (20). To test the hypothesis that posttranslational sulfation of ACA-01 modulates its binding affinity for these chemokines, we used a competitive fluorescence anisotropy assay (36), which monitored the ability of evasins 1-4 to displace fluorescein-labeled, receptor-derived sulfopeptides (36,37) from the target chemokines (SI Appendix, Figs. S21 and S22).…”

Section: Resultsmentioning

confidence: 99%

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

Franck

Foster

Johansen-Leete

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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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 theAmblyomma cajennensetick 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.

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“…Inspired by the applications of thiolated amino acids in NCL, Payne and co‐workers also reported the synthesis of selenolated amino acid building blocks, such as Asp, Glu, Leu, Phe, and Pro (Figure ). As in NCL, peptides bearing selenolated amino acids at their N ‐termini could also ligate peptide selenoesters.…”

Section: Other Ligation Techniquesmentioning

confidence: 99%

Chemical Protein Synthesis by Native Chemical Ligation and Variations Thereof

et al. 2019

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For a long time, the total synthesis of proteins was considered as a “mission impossible” because of the tedious and complex synthetic steps and demanding purification processes. However, with the development of modern synthetic methodologies, many protein syntheses have now been reported. More importantly, through chemical synthesis, desired modifications can be installed to target proteins precisely, which is a major advantage over traditional bio‐synthesis approaches. This review summarizes the techniques developed for protein assembly, including native chemical ligation, Se‐mediated ligation, and a range of other ligation methods. A few synthetic examples, whereby synthetic proteins with desired modifications have been utilized for related biological research, are also included. We believe that chemical synthesis can provide alternative pathways to solve problems that have hitherto proved insurmountable by traditional biological approaches.

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Sulfation of the Human Cytomegalovirus Protein UL22A Enhances Binding to the Chemokine RANTES

Cited by 12 publications

References 42 publications

Ticks from diverse genera encode chemokine-inhibitory evasin proteins

Ticks from diverse genera encode chemokine-inhibitory evasin proteins

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

Chemical Protein Synthesis by Native Chemical Ligation and Variations Thereof

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