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Cell Rep . Super-resolution proximity labeling reveals anti-viral protein network and its structural changes against SARS-CoV-2 viral proteins

tetano

Editor, Senior Moderator
Cell Rep


. 2023 Jul 20;42(8):112835.
doi: 10.1016/j.celrep.2023.112835. Online ahead of print. Super-resolution proximity labeling reveals anti-viral protein network and its structural changes against SARS-CoV-2 viral proteins

Yun-Bin Lee[SUP] 1 [/SUP], Minkyo Jung[SUP] 2 [/SUP], Jeesoo Kim[SUP] 3 [/SUP], Afandi Charles[SUP] 4 [/SUP], Wanda Christ[SUP] 5 [/SUP], Jiwoong Kang[SUP] 1 [/SUP], Myeong-Gyun Kang[SUP] 1 [/SUP], Chulhwan Kwak[SUP] 1 [/SUP], Jonas Klingström[SUP] 6 [/SUP], Anna Smed-Sörensen[SUP] 4 [/SUP], Jong-Seo Kim[SUP] 7 [/SUP], Ji Young Mun[SUP] 8 [/SUP], Hyun-Woo Rhee[SUP] 9 [/SUP]



Affiliations
Free article Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in human cells by interacting with host factors following infection. To understand the virus and host interactome proximity, we introduce a super-resolution proximity labeling (SR-PL) method with a "plug-and-playable" PL enzyme, TurboID-GBP (GFP-binding nanobody protein), and we apply it for interactome mapping of SARS-CoV-2 ORF3a and membrane protein (M), which generates highly perturbed endoplasmic reticulum (ER) structures. Through SR-PL analysis of the biotinylated interactome, 224 and 272 peptides are robustly identified as ORF3a and M interactomes, respectively. Within the ORF3a interactome, RNF5 co-localizes with ORF3a and generates ubiquitin modifications of ORF3a that can be involved in protein degradation. We also observe that the SARS-CoV-2 infection rate is efficiently reduced by the overexpression of RNF5 in host cells. The interactome data obtained using the SR-PL method are presented at https://sarscov2.spatiomics.org. We hope that our method will contribute to revealing virus-host interactions of other viruses in an efficient manner.

Keywords: CP: Microbiology; ER; ER stress; MS; SR-PL; endoplasmic reticulum; endoplasmic reticulum stress; mass spectrometry; mitochondria; super-resolution proximity labeling; virus.

 
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