Host PDZ-containing proteins targeted by SARS-CoV-2.

[en] 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.

Disciplines :

Immunology & infectious disease

Author, co-author :

Caillet-Saguy, Célia

Durbesson, Fabien

Rezelj, Veronica V.

Gogl, Gergö

Tran, Quang Dinh

Twizere, Jean-Claude ; Université de Liège - ULiège > GIGA Molecul. Bio. of Diseases - Viral Interactomes Network

Vignuzzi, Marco

Vincentelli, Renaud

Wolff, Nicolas

Language :

English

Title :

Host PDZ-containing proteins targeted by SARS-CoV-2.

Publication date :

2021

Journal title :

FEBS Journal

ISSN :

1742-464X

eISSN :

1742-4658

Publisher :

Blackwell, Oxford, United Kingdom

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 22 November 2021

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