Host PDZ-containing proteins targeted by SARS-CoV-2.
Célia Caillet-SaguyFabien DurbessonVeronica V RezeljGergö GoglQuang Dinh TranJean-Claude TwizereMarco VignuzziRenaud VincentelliNicolas WolffPublished in: The FEBS journal (2021)
Small linear motifs targeting protein interacting domains called PSD-95/Dlg/ZO-1 (PDZ) have been identified at the C terminus of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins E, 3a, and N. Using a high-throughput approach of affinity-profiling against the full human PDZome, we identified sixteen human PDZ binders of SARS-CoV-2 proteins E, 3A, and N showing significant interactions with dissociation constants values ranging from 3 to 82 μm. Six of them (TJP1, PTPN13, HTRA1, PARD3, MLLT4, LNX2) are also recognized by SARS-CoV while three (NHERF1, MAST2, RADIL) are specific to SARS-CoV-2 E protein. Most of these SARS-CoV-2 protein partners are involved in cellular junctions/polarity and could be also linked to evasion mechanisms of the immune responses during viral infection. Among the binders of the SARS-CoV-2 proteins E, 3a, or N, seven significantly affect viral replication under knock down gene expression in infected cells. This PDZ profiling identifying human proteins potentially targeted by SARS-CoV-2 can help to understand the multifactorial severity of COVID19 and to conceive effective anti-coronaviral agents for therapeutic purposes.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- endothelial cells
- gene expression
- immune response
- high throughput
- cancer therapy
- dna methylation
- induced pluripotent stem cells
- single cell
- binding protein
- induced apoptosis
- cell proliferation
- protein protein
- amino acid
- signaling pathway
- oxidative stress
- drug delivery
- mass spectrometry
- single molecule
- toll like receptor
- cell cycle arrest
- protein kinase
- antiretroviral therapy
- hiv infected