Regulation of the trafficking and antiviral activity of IFITM3 by post-translational modifications.
Regulation of the trafficking and antiviral activity of IFITM3 by post-translational modifications.
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DOI：
10.2217/fmb.14.65
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发表时间：
2014
影响因子：
3.1
通讯作者：
Yount JS
中科院分区：
文献类型：
--
作者：
Chesarino NM;McMichael TM;Yount JS
IFITM 3限制多种重要病毒病原体的细胞感染，并且对于针对流感病毒的先天免疫应答特别关键。IFITM 3的表达扩大酸性内溶酶体区室并阻止内吞病毒的融合，导致其降解。这种小的，133个氨基酸的抗病毒蛋白由至少四种不同的翻译后修饰控制。IFITM 3抗病毒活性的正调节由S-棕榈酰化提供，而负调节机制包括赖氨酸泛素化、赖氨酸甲基化和酪氨酸磷酸化。在这里，我们描述了具体的见解IFITM 3的运输和活动，提供了IFITM 3的翻译后修饰的研究，并讨论了证据表明，IFITM 3采用多个膜拓扑结构，涉及至少一个膜内结构域在其抗病毒活性构象。
IFITM3 restricts cellular infection by multiple important viral pathogens, and is particularly critical for the innate immune response against influenza virus. Expression of IFITM3 expands acidic endolysosomal compartments and prevents fusion of endocytosed viruses, leading to their degradation. This small, 133 amino acid, antiviral protein is controlled by at least four distinct post-translational modifications. Positive regulation of IFITM3 antiviral activity is provided by S-palmitoylation, while negative regulatory mechanisms include lysine ubiquitination, lysine methylation and tyrosine phosphorylation. Herein, we describe specific insights into IFITM3 trafficking and activity that were provided by studies of IFITM3 post-translational modifications, and discuss evidence suggesting that IFITM3 adopts multiple membrane topologies involving at least one intramembrane domain in its antivirally active conformation.