Dept. of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, 12801 East 17th Ave, Aurora, CO, 80045, USA.
Alzheimer's Research UK Oxford Drug Discovery Institute, NDM Research Building, University of Oxford Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, USA.
Sci Rep. 2020 Feb 24;10(1):3300. doi: 10.1038/s41598-020-60242-9.
Aedes aegypti is the primary vector for transmission of Dengue, Zika and chikungunya viruses. Previously it was shown that Dengue virus infection of the mosquito led to an in increased expression of the odorant binding protein 22 (AeOBP22) within the mosquito salivary gland and that siRNA mediated knockdown of AeOBP22 led to reduced mosquito feeding behaviors. Insect OBPs are implicated in the perception, storage and transport of chemosensory signaling molecules including air-borne odorants and pheromones. AeOBP22 is unusual as it is additionally expressed in multiple tissues, including the antenna, the male reproductive glands and is transferred to females during reproduction, indicating multiple roles in the mosquito life cycle. However, it is unclear what role it plays in these tissues and what ligands it interacts with. Here we present solution and X-ray crystallographic studies that indicate a potential role of AeOBP22 binding to fatty acids, and that the specificity for longer chain fatty acids is regulated by a conformational change in the C-terminal tail that leads to creation of an enlarged binding cavity that enhances binding affinity. This study sheds light onto the native ligands for AeOBP22 and provides insight into its potential functions in different tissues.
埃及伊蚊是登革热、寨卡和基孔肯雅热病毒的主要传播媒介。先前的研究表明，登革热病毒感染蚊子会导致蚊子唾液腺中气味结合蛋白 22（AeOBP22）的表达增加，而 AeOBP22 的 siRNA 介导敲低会导致蚊子摄食行为减少。昆虫 OBPs 参与包括空气传播气味和信息素在内的化学感觉信号分子的感知、储存和运输。AeOBP22 是不寻常的，因为它还在多个组织中表达，包括触角、雄性生殖腺，并在繁殖期间转移到雌性，这表明它在蚊子的生命周期中具有多种作用。然而，它在这些组织中扮演什么角色以及与什么配体相互作用尚不清楚。在这里，我们提出了溶液和 X 射线晶体学研究，表明 AeOBP22 与脂肪酸结合的潜在作用，并且通过 C 末端尾部的构象变化来调节对长链脂肪酸的特异性，这导致形成扩大的结合腔，从而增强结合亲和力。这项研究揭示了 AeOBP22 的天然配体，并为其在不同组织中的潜在功能提供了深入了解。
