ADP binding by the Culex quinquefasciatus mosquito D7 salivary protein enhances blood feeding on mammals
ADP binding by the Culex quinquefasciatus mosquito D7 salivary protein enhances blood feeding on mammals
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致倦库蚊D7唾液蛋白与ADP的结合增强对哺乳动物的摄血作用
DOI：
10.1038/s41467-020-16665-z
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发表时间：
2020-06-09
影响因子：
16.6
通讯作者：
Calvo, Eric
中科院分区：
文献类型：
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作者：
Martin-Martin, Ines;Paige, Andrew;Calvo, Eric
在吸血过程中，蚊子的唾液被注射到皮肤中，以促进吸血。D 7蛋白是蚊子唾液中最丰富的成分之一。在这里，我们报告的配体结合特异性和生理相关性的两个D 7长蛋白从致倦库蚊，丝虫寄生虫或西尼罗河病毒的载体。CxD 7 L2结合生物胺和类花生酸。CxD 7 L1表现出对ADP和ATP的高亲和力，这是任何D 7中都没有报道的结合能力。我们解决了CxD 7 L1与ADP的复合物的晶体结构，分辨率为1.97埃。结合口袋位于两个蛋白质结构域之间，而所有已知的D 7结合N-或C-末端结构域内的配体。我们证明了这些蛋白质在离体和体内实验中抑制止血。我们的研究结果表明，ADP结合功能获得CxD 7 L1进化，以提高哺乳动物的血液喂养，其中ADP在血小板聚集中起着关键作用。D 7蛋白在几种吸血昆虫的唾液腺中含量很高。在这里，作者研究了蚊子D 7蛋白CxD 7 L1和CxD 7 L2的配体结合特异性和生理作用，表明CxD 7 L1获得ADP结合特性，以增强哺乳动物的血液喂养。
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 angstrom resolution. The binding pocket lies between the two protein domains, whereas all known D7s bind ligands either within the N- or 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. D7 proteins are highly abundant in the salivary glands of several blood feeding insects. Here, the authors study the ligand binding specificity and physiological roles of the mosquito D7 proteins CxD7L1 and CxD7L2, showing that CxD7L1 acquired ADP-binding properties to enhance blood feeding in mammals.