Host PDZ-containing proteins targeted by SARS-CoV-2.
Fiche publication
Date publication
septembre 2021
Journal
The FEBS journal
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GOGL Gergo
Tous les auteurs :
Caillet-Saguy C, Durbesson F, Rezelj VV, Gogl G, Tran QD, Twizere JC, Vignuzzi M, Vincentelli R, Wolff N
Lien Pubmed
Résumé
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.
Mots clés
3A and N, PDZ-binding motif, PDZ-containing protein, SARS-CoV-2, human PDZ library, viral proteins E, viral replication
Référence
FEBS J. 2021 09;288(17):5148-5162