During blood-feeding, mosquito saliva is injected into the skin to facilitate blood meal acquisition. D7 proteins are among the most abundant components of the mosquito saliva. Here we report the ligand binding specificity and physiological relevance of two D7 long proteins from Culex quinquefasciatus mosquito, the vector of filaria parasites or West Nile viruses. CxD7L2 binds biogenic amines and eicosanoids. CxD7L1 exhibits high affinity for ADP and ATP, a binding capacity not reported in any D7. We solve the crystal structure of CxD7L1 in complex with ADP to 1.97 Å resolution. The binding pocket lies between the two protein domains, whereas all known D7s bind ligands either within the Nor the C-terminal domains. We demonstrate that these proteins inhibit hemostasis in ex vivo and in vivo experiments. Our results suggest that the ADP-binding function acquired by CxD7L1 evolved to enhance blood-feeding in mammals, where ADP plays a key role in platelet aggregation.
When a mosquito inserts its mouth parts into the host skin, it causes tissue and vascular damage that triggers host hemostatic responses. Mosquito saliva is injected at the bite site to counteract the hemostasis and help blood‐feeding. D7 salivary proteins bind and scavenge several hemostasis agonists such as serotonin, norepinephrine, and U‐46619. Therefore, D7 proteins inhibit the action of the host molecules and prevent vasoconstriction and platelet aggregation.
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