Site-Specific Photo-Crosslinking Proteomics Reveal Regulation of IFITM3 Trafficking and Turnover by VCP/p97 ATPase

被引：25

作者：

Wu, Xiaojun ^{[1
]}

Spence, Jennifer S. ^{[2
]}

Das, Tandrila ^{[3
]}

Yuan, Xiaoqiu ^{[3
]}

Chen, Chengjie ^{[1
]}

Zhang, Yuqing ^{[1
]}

Li, Yumeng ^{[1
]}

Sun, Yanan ^{[1
]}

Chandran, Kartik ^{[2
]}

Hang, Howard C. ^{[3
]}

Peng, Tao ^{[1
]}

机构：

[1] Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, State Key Lab Chem Oncogen, Shenzhen 518055, Peoples R China

[2] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA

[3] Rockefeller Univ, Lab Chem Biol & Microbial Pathogenesis, New York, NY 10065 USA

来源：

CELL CHEMICAL BIOLOGY | 2020年 / 27卷 / 05期

基金：

中国国家自然科学基金;

关键词：

PROTEIN-PROTEIN INTERACTIONS; INFLUENZA-A VIRUS; N-TERMINAL REGION; WEST NILE VIRUS; ANTIVIRAL ACTIVITY; MEMBRANE-PROTEINS; S-PALMITOYLATION; CELL-CULTURE; AMINO-ACIDS; INFECTION;

D O I：

10.1016/j.chembiol.2020.03.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Interferon-induced transmembrane protein 3 (IFITM3) is a key interferon effector that broadly prevents infection by diverse viruses. However, the cellular factors that control IFITM3 homeostasis and antiviral activity have not been fully elucidated. Using site-specific photo-crosslinking and quantitative proteomic analysis, here we present the identification and functional characterization of VCP/p97 AAA-ATPase as a primary interaction partner of IFITM3. We show that IFITM3 ubiquitination at lysine 24 is crucial for VCP binding, trafficking, turnover, and engagement with incoming virus particles. Consistently, pharmacological inhibition of VCP/p97 ATPase activity leads to defective IFITM3 lysosomal sorting, turnover, and co-trafficking with virus particles. Our results showcase the utility of site-specific protein photo-crosslinking in mammalian cells and reveal VCP/p97 as a key cellular factor involved in IFITM3 trafficking and homeostasis.

引用

页码：571 / +

页数：21

共 94 条

[1] Probing Protein-Protein Interactions with a Genetically Encoded Photo-crosslinking Amino Acid [J].