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Host PDZ‐containing proteins targeted by SARS‐CoV‐2

Abstract : 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.
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Contributor : Célia Caillet-Saguy <>
Submitted on : Sunday, May 2, 2021 - 5:37:30 PM
Last modification on : Wednesday, June 23, 2021 - 11:34:01 AM

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Célia Caillet-Saguy, Fabien Durbesson, Veronica Rezelj, Gergö Gogl, Quang Dinh Tran, et al.. Host PDZ‐containing proteins targeted by SARS‐CoV‐2. FEBS Journal, Wiley, 2021, ⟨10.1111/febs.15881⟩. ⟨pasteur-03214719⟩



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