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人类ANP32A/B会发生SUMO化修饰,并被禽流感病毒NS2蛋白利用以克服物种特异性限制。

Human ANP32A/B are SUMOylated and utilized by avian influenza virus NS2 protein to overcome species-specific restriction.

作者信息

Sun Liuke, Guo Xing, Yu Mengmeng, Wang Xue-Feng, Ren Huiling, Wang Xiaojun

机构信息

State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China.

Institute of Western Agriculture, The Chinese Academy of Agricultural Sciences, Changji, China.

出版信息

Nat Commun. 2024 Dec 30;15(1):10805. doi: 10.1038/s41467-024-55034-y.

DOI:10.1038/s41467-024-55034-y
PMID:39737943
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11686252/
Abstract

Human ANP32A/B (huANP32A/B) poorly support the polymerase activity of avian influenza viruses (AIVs), thereby limiting interspecies transmission of AIVs from birds to humans. The SUMO-interacting motif (SIM) within NS2 promotes the adaptation of AIV polymerase to huANP32A/B via a yet undisclosed mechanism. Here we show that huANP32A/B are SUMOylated by the E3 SUMO ligase PIAS2α, and deSUMOylated by SENP1. SUMO modification of huANP32A/B results in the recruitment of NS2, thereby facilitating huANP32A/B-supported AIV polymerase activity. Such a SUMO-dependent recruitment of NS2 is mediated by its association with huANP32A/B via the SIM-SUMO interaction module, where K68/K153-SUMO in huANP32A or K68/K116-SUMO in huANP32B interacts with the NS2-SIM. The SIM-SUMO-mediated interactions between NS2 and huANP32A/B function to promote AIV polymerase activity by positively regulating AIV vRNP-huANP32A/B interactions and AIV vRNP assembly. Our study offers insights into the mechanism of NS2-SIM in facilitating AIVs adaptation to mammals.

摘要

人类ANP32A/B(huANP32A/B)对禽流感病毒(AIV)的聚合酶活性支持较差,从而限制了AIV从鸟类到人类的跨物种传播。NS2中的小泛素样修饰蛋白(SUMO)相互作用基序(SIM)通过一种尚未公开的机制促进AIV聚合酶对huANP32A/B的适应。在此,我们表明huANP32A/B被E3 SUMO连接酶PIAS2α进行SUMO化修饰,并被SENP1去SUMO化。huANP32A/B的SUMO修饰导致NS2的募集,从而促进huANP32A/B支持的AIV聚合酶活性。NS2的这种SUMO依赖性募集是通过其与huANP32A/B通过SIM-SUMO相互作用模块的结合介导的,其中huANP32A中的K68/K153-SUMO或huANP32B中的K68/K116-SUMO与NS2-SIM相互作用。NS2与huANP32A/B之间的SIM-SUMO介导的相互作用通过正向调节AIV病毒核糖核蛋白(vRNP)-huANP32A/B相互作用和AIV vRNP组装来促进AIV聚合酶活性。我们的研究为NS2-SIM促进AIV适应哺乳动物的机制提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/ef9e28d73dfe/41467_2024_55034_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/1810813990e9/41467_2024_55034_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/04adf6590f6d/41467_2024_55034_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/f32ea576d263/41467_2024_55034_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/e35ab2b08b4a/41467_2024_55034_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/450f51299bf0/41467_2024_55034_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/c37bdd7de5c4/41467_2024_55034_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/8c720c49ed87/41467_2024_55034_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/e677802b5685/41467_2024_55034_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/ef9e28d73dfe/41467_2024_55034_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/1810813990e9/41467_2024_55034_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/04adf6590f6d/41467_2024_55034_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/f32ea576d263/41467_2024_55034_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/e35ab2b08b4a/41467_2024_55034_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/450f51299bf0/41467_2024_55034_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/c37bdd7de5c4/41467_2024_55034_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/8c720c49ed87/41467_2024_55034_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/e677802b5685/41467_2024_55034_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/858b/11686252/ef9e28d73dfe/41467_2024_55034_Fig9_HTML.jpg

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