ERManI (Endoplasmic Reticulum Class I alpha-Mannosidase) Is Required for HIV-1 Envelope Glycoprotein Degradation via Endoplasmic Reticulum-associated Protein Degradation Pathway

文献类型： 外文期刊

第一作者： Zhou, Tao

作者： Zhou, Tao;Zheng, Yong-Hui;Moremen, Kelley W.;Zhou, Tao;Frabutt, Dylan A.;Zheng, Yong-Hui;Zhou, Tao;Frabutt, Dylan A.;Zheng, Yong-Hui

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期刊名称：JOURNAL OF BIOLOGICAL CHEMISTRY （ 影响因子：5.157； 五年影响因子：5.041 ）

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收录情况： SCI

摘要： Previously, we reported that the mitochondrial translocator protein (TSPO) induces HIV-1 envelope (Env) degradation via the endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway, but the mechanism was not clear. Here we investigated how the four ER-associated glycoside hydrolase family 47 (GH47) alpha-mannosidases, ERManI, and ER-degradation enhancing alpha-mannosidase-like (EDEM) proteins 1, 2, and 3, are involved in the Env degradation process. Ectopic expression of these four alpha-mannosidases uncovers that only ERManI inhibits HIV-1 Env expression in a dose-dependent manner. In addition, genetic knock-out of the ERManI gene MAN1B1 using CRISPR/Cas9 technology disrupts the TSPO-mediated Env degradation. Biochemical studies show that HIV-1 Env interacts with ERManI, and between the ERManI cytoplasmic, transmembrane, lumenal stem, and lumenal catalytic domains, the catalytic domain plays a critical role in the Env-ERManI interaction. In addition, functional studies show that inactivation of the catalytic sites by site-directed mutagenesis disrupts the ERManI activity. These studies identify ERManI as a critical GH47 alpha-mannosidase in the ER-associated protein degradation pathway that initiates the Env degradation and suggests that its catalytic domain and enzymatic activity play an important role in this process.

分类号： Q5

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