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DOI10.1073/pnas.2019251118
The mosquito protein AEG12 displays both cytolytic and antiviral properties via a common lipid transfer mechanism
Foo A.C.Y.; Thompson P.M.; Chen S.-H.; Jadi R.; Lupo B.; DeRose E.F.; Arora S.; Placentra V.C.; Premkumar L.; Perera L.; Pedersen L.C.; Martin N.; Mueller G.A.
发表日期2021
ISSN00278424
卷号118期号:11
英文摘要The mosquito protein AEG12 is up-regulated in response to blood meals and flavivirus infection though its function remained elusive. Here, we determine the three-dimensional structure of AEG12 and describe the binding specificity of acyl-chain ligands within its large central hydrophobic cavity. We show that AEG12 displays hemolytic and cytolytic activity by selectively delivering unsaturated fatty acid cargoes into phosphatidylcholine-rich lipid bilayers. This property of AEG12 also enables it to inhibit replication of enveloped viruses such as Dengue and Zika viruses at low micromolar concentrations. Weaker inhibition was observed against more distantly related coronaviruses and lentivirus, while no inhibition was observed against the nonenveloped virus adeno-associated virus. Together, our results uncover the mechanistic understanding of AEG12 function and provide the necessary implications for its use as a broadspectrum therapeutic against cellular and viral targets. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Antiviral; Cytolysis; Insect digestion; Insect immune response; Membrane disruption
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180244
作者单位Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle ParkNC 27709, United States; Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle ParkNC 27709, United States; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, United States
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Foo A.C.Y.,Thompson P.M.,Chen S.-H.,et al. The mosquito protein AEG12 displays both cytolytic and antiviral properties via a common lipid transfer mechanism[J],2021,118(11).
APA Foo A.C.Y..,Thompson P.M..,Chen S.-H..,Jadi R..,Lupo B..,...&Mueller G.A..(2021).The mosquito protein AEG12 displays both cytolytic and antiviral properties via a common lipid transfer mechanism.Proceedings of the National Academy of Sciences of the United States of America,118(11).
MLA Foo A.C.Y.,et al."The mosquito protein AEG12 displays both cytolytic and antiviral properties via a common lipid transfer mechanism".Proceedings of the National Academy of Sciences of the United States of America 118.11(2021).
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