6QJB
Truncated Evasin-3 (tEv3 17-56)
Summary for 6QJB
| Entry DOI | 10.2210/pdb6qjb/pdb |
| NMR Information | BMRB: 34354 |
| Descriptor | Evasin-3 (1 entity in total) |
| Functional Keywords | chemokine-binding protein, ticks, immune system |
| Biological source | Rhipicephalus sanguineus (Brown dog tick) |
| Total number of polymer chains | 1 |
| Total formula weight | 4314.92 |
| Authors | Denisov, S.S.,Ippel, J.H.,Heinzman, A.C.A.,Koenen, R.R.,Ortega-Gomez, A.,Soehnlein, O.,Hackeng, T.M.,Dijkgraaf, I. (deposition date: 2019-01-24, release date: 2019-07-03, Last modification date: 2024-10-09) |
| Primary citation | Denisov, S.S.,Ippel, J.H.,Heinzmann, A.C.A.,Koenen, R.R.,Ortega-Gomez, A.,Soehnlein, O.,Hackeng, T.M.,Dijkgraaf, I. Tick saliva protein Evasin-3 modulates chemotaxis by disrupting CXCL8 interactions with glycosaminoglycans and CXCR2. J.Biol.Chem., 294:12370-12379, 2019 Cited by PubMed Abstract: Chemokines are a group of chemotaxis proteins that regulate cell trafficking and play important roles in immune responses and inflammation. Ticks are blood-sucking parasites that secrete numerous immune-modulatory agents in their saliva to evade host immune responses. Evasin-3 is a small salivary protein that belongs to a class of chemokine-binding proteins isolated from the brown dog tick, Evasin-3 has been shown to have a high affinity for chemokines CXCL1 and CXCL8 and to diminish inflammation in mice. In the present study, solution NMR spectroscopy was used to investigate the structure of Evasin-3 and its CXCL8-Evasin-3 complex. Evasin-3 is found to disrupt the glycosaminoglycan-binding site of CXCL8 and inhibit the interaction of CXCL8 with CXCR2. Structural data were used to design two novel CXCL8-binding peptides. The linear tEv3 17-56 and cyclic tcEv3 16-56 dPG Evasin-3 variants were chemically synthesized by solid-phase peptide synthesis. The affinity of these newly synthesized variants to CXCL8 was measured by surface plasmon resonance biosensor analysis. The values of tEv3 17-56 and tcEv3 16-56 dPG were 27 and 13 nm, respectively. Both compounds effectively inhibited CXCL8-induced migration of polymorphonuclear neutrophils. The present results suggest utility of synthetic Evasin-3 variants as scaffolds for designing and fine-tuning new chemokine-binding agents that suppress immune responses and inflammation. PubMed: 31235521DOI: 10.1074/jbc.RA119.008902 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
