Host PDZ-containing proteins targeted by SARS-Cov-2

Abstract Small linear motif targeting protein interacting domains called 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 iden...

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Published inbioRxiv
Main Authors Caillet-Saguy, Célia, Durbesson, Fabien, Rezelj, Veronica V, Gogl, Gergö, Quang Dinh Tran, Twizere, Jean-Claude, Vignuzzi, Marco, Vincentelli, Renaud, Wolff, Nicolas
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 01.02.2021
Subjects
C-Terminus
Coronaviruses
COVID-19
E protein
Gene expression
Immune response
Polarity
Proteins
Severe acute respiratory syndrome coronavirus 2
Therapeutic applications
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Summary:Abstract Small linear motif targeting protein interacting domains called 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 μM 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. Seven of the PDZ-containing proteins among binders of the SARS-CoV-2 proteins E, 3a or N affect significantly 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. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.02.01.429176