A knottin scaffold directs the CXC-chemokine-binding specificity of tick evasins.

ABSTRACT: Tick evasins (EVAs) bind either CC- or CXC-chemokines by a poorly understood promiscuous or "one-to-many" mechanism to neutralize inflammation. Because EVAs potently inhibit inflammation in many preclinical models, highlighting their potential as biological therapeutics for inflammatory diseases, we sought to further unravel the CXC-chemokine-EVA interactions. Using yeast surface display, we identified and characterized 27 novel CXC-chemokine-binding evasins homologous to EVA3 and defined two functional classes. The first, which included EVA3, exclusively bound ELR⁺ CXC-chemokines, whereas the second class bound both ELR⁺ and ELR^- CXC-chemokines, in several cases including CXC-motif chemokine ligand 10 (CXCL10) but, surprisingly, not CXCL8. The X-ray

SUBMITTER: Lee AW 

PROVIDER: S-EPMC6643034 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature