Host PDZ-containing proteins targeted by SARS-CoV-2 #MMPMID33864728
Caillet-Saguy C; Durbesson F; Rezelj VV; Gogl G; Tran QD; Twizere JC; Vignuzzi M; Vincentelli R; Wolff N
FEBS J 2021[Sep]; 288 (17): 5148-5162 PMID33864728show ga
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 mum. 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.
|COVID-19/*genetics/virology[MESH]
|Carrier Proteins/genetics[MESH]
|Coronavirus Nucleocapsid Proteins/genetics[MESH]
|Host-Pathogen Interactions/*genetics[MESH]
|Humans[MESH]
|Kinesins/genetics[MESH]
|Myosins/genetics[MESH]
|PDZ Domains/*genetics[MESH]
|Protein Binding/genetics[MESH]
|Protein Interaction Domains and Motifs/genetics[MESH]
|Protein Tyrosine Phosphatase, Non-Receptor Type 13/genetics[MESH]
free
free
free
FEBS+J 2021 ; 288 (17): 5148-5162
