7so0

Crystal Structure of the Engineered Tick Evasin EVA-P974(F31A) Complexed to Human Chemokine CCL2Crystal Structure of the Engineered Tick Evasin EVA-P974(F31A) Complexed to Human Chemokine CCL2

Structural highlights

7so0 is a 2 chain structure with sequence from Amblyomma cajennense and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.74Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EV974_AMBCJ Salivary chemokine-binding protein which binds to host chemokines CCL1, CCL3, CCL4, CCL8, CCL17, CCL18 and CCL22.^[1]

Publication Abstract from PubMed

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.

Structure-guided engineering of tick evasins for targeting chemokines in inflammatory diseases.,Bhusal RP, Aryal P, Devkota SR, Pokhrel R, Gunzburg MJ, Foster SR, Lim HD, Payne RJ, Wilce MCJ, Stone MJ Proc Natl Acad Sci U S A. 2022 Mar 1;119(9). pii: 2122105119. doi:, 10.1073/pnas.2122105119. PMID:35217625^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Singh K, Davies G, Alenazi Y, Eaton JRO, Kawamura A, Bhattacharya S. Yeast surface display identifies a family of evasins from ticks with novel polyvalent CC chemokine-binding activities. Sci Rep. 2017 Jun 27;7(1):4267. PMID:28655871 doi:10.1038/s41598-017-04378-1
↑ Bhusal RP, Aryal P, Devkota SR, Pokhrel R, Gunzburg MJ, Foster SR, Lim HD, Payne RJ, Wilce MCJ, Stone MJ. Structure-guided engineering of tick evasins for targeting chemokines in inflammatory diseases. Proc Natl Acad Sci U S A. 2022 Mar 1;119(9). pii: 2122105119. doi:, 10.1073/pnas.2122105119. PMID:35217625 doi:http://dx.doi.org/10.1073/pnas.2122105119

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OCA

[1] Singh K, Davies G, Alenazi Y, Eaton JRO, Kawamura A, Bhattacharya S. Yeast surface display identifies a family of evasins from ticks with novel polyvalent CC chemokine-binding activities. Sci Rep. 2017 Jun 27;7(1):4267. PMID:28655871 doi:10.1038/s41598-017-04378-1

[2] Bhusal RP, Aryal P, Devkota SR, Pokhrel R, Gunzburg MJ, Foster SR, Lim HD, Payne RJ, Wilce MCJ, Stone MJ. Structure-guided engineering of tick evasins for targeting chemokines in inflammatory diseases. Proc Natl Acad Sci U S A. 2022 Mar 1;119(9). pii: 2122105119. doi:, 10.1073/pnas.2122105119. PMID:35217625 doi:http://dx.doi.org/10.1073/pnas.2122105119

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