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

Caillet-Saguy, C.; Durbesson, F.; REZELJ, V. V.; Gogl, G.; Tran, Q. D.; Twizere, J.-C.; Vignuzzi, M.; Vincentelli, R.; Wolff, N.

doi:10.1101/2021.02.01.429176

bioRxiv · 10.1101/2021.02.01.429176

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

Caillet-Saguy, C.·Durbesson, F.·REZELJ, V. V.·Gogl, G.·Tran, Q. D.·Twizere, J.-C.·Vignuzzi, M.·Vincentelli, R.·Wolff, N.

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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 M to 82 M. 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.

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Caillet-Saguy, C., Durbesson, F., REZELJ, V. V., Gogl, G., Tran, Q. D., Twizere, J.-C., Vignuzzi, M., Vincentelli, R., Wolff, N.. 2021-02-01. Host PDZ-containing proteins targeted by SARS-Cov-2. https://doi.org/10.1101/2021.02.01.429176

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