Understanding the molecular basis of how the chemokine network is targeted by evasin proteins from tick saliva

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Chemokines are small, secreted proteins that are major drivers of inflammation, functioning via binding to GPCRs to recruit immune-inflammatory cells to damaged tissues. Ticks secrete small proteins called evasins, in saliva, that have the ability to bind and neutralise multiple chemokines, thus disabling the host chemokine network. This property allows ticks to feed for days without detection. Evasins have been shown to have potent anti-inflammatory effects in preclinical models, including in myocardial infarction and plaque inflammation. Over 40 tick evasins from multiple tick species have been identified to date, all with broad and promiscuous chemokine binding properties. We aim to study the properties of the interaction interfaces between evasins and chemokines using chemical and structural biology techniques. Protein fragments will be employed to understand the molecular basis of the multi-chemokine binding properties of evasins, and to investigate how evasins neutralise chemokine function. We also aim to understand more about the selectivity of these interactions through modification of fragments/proteins by chemical synthesis, expanding our rationale for chemical probe development. By mapping these protein-protein interactions using these chemical probes we hope to gain an understanding of how these interactions might be mimicked.