7S4N
Crystal structure of the tick evasin EVA-P974 complexed to human chemokine CCL17
Summary for 7S4N
| Entry DOI | 10.2210/pdb7s4n/pdb |
| Descriptor | Evasin P974, C-C motif chemokine 17 (3 entities in total) |
| Functional Keywords | inflammation, evasin, chemokine, evasion-chemokine complex, immune system |
| Biological source | Amblyomma cajennense (Cayenne tick, Acarus cajennensis) More |
| Total number of polymer chains | 4 |
| Total formula weight | 35596.74 |
| Authors | Bhusal, R.P.,Devkota, S.R.,Aryal, P.,Wilce, M.C.J.,Stone, M.J. (deposition date: 2021-09-09, release date: 2022-03-16, Last modification date: 2024-10-16) |
| Primary citation | Bhusal, R.P.,Aryal, P.,Devkota, S.R.,Pokhrel, R.,Gunzburg, M.J.,Foster, S.R.,Lim, H.D.,Payne, R.J.,Wilce, M.C.J.,Stone, M.J. Structure-guided engineering of tick evasins for targeting chemokines in inflammatory diseases. Proc.Natl.Acad.Sci.USA, 119:-, 2022 Cited by PubMed Abstract: As natural chemokine inhibitors, evasin proteins produced in tick saliva are potential therapeutic agents for numerous inflammatory diseases. Engineering evasins to block the desired chemokines and avoid off-target side effects requires structural understanding of their target selectivity. Structures of the class A evasin EVA-P974 bound to human CC chemokine ligands 7 and 17 (CCL7 and CCL17) and to a CCL8-CCL7 chimera reveal that the specificity of class A evasins for chemokines of the CC subfamily is defined by conserved, rigid backbone-backbone interactions, whereas the preference for a subset of CC chemokines is controlled by side-chain interactions at four hotspots in flexible structural elements. Hotspot mutations alter target preference, enabling inhibition of selected chemokines. The structure of an engineered EVA-P974 bound to CCL2 reveals an underlying molecular mechanism of EVA-P974 target preference. These results provide a structure-based framework for engineering evasins as targeted antiinflammatory therapeutics. PubMed: 35217625DOI: 10.1073/pnas.2122105119 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
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