Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

CC and CXC-chemokines are the primary drivers of chemotaxis in inflamma- tion, but chemokine network redundancy thwarts pharmacological interven- tion. Tick evasins promiscuously bind CC and CXC-chemokines, overcoming redundancy. Here we show that short peptides that promiscuously bind both chemokine classes can be identified from evasins by phage-display screening performed with multiple chemokines in parallel. We identify two conserved motifs within these peptides and show using saturation-mutagenesis phage- display and chemotaxis studies of an exemplar peptide that an anionic patch in the first motif and hydrophobic, aromatic and cysteine residues in the second are functionally necessary. AlphaFold2-Multimer modelling suggests that the peptide occludes distinct receptor-binding regions in CC and in CXC-chemo- kines, with the first and second motifs contributing ionic and hydrophobic interactions respectively. Our results indicate that peptides with broad- spectrum anti-chemokine activity and therapeutic potential may be identified from evasins, and the pharmacophore characterised by phage display, saturation mutagenesis and computational modelling.

Original publication

DOI

10.1038/s41467-023-41488-z

Type

Journal article

Journal

Nature Communications

Publisher

Springer Science and Business Media LLC

Publication Date

16/09/2023

Volume

14