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Host PDZ‐containing proteins targeted by SARS‐CoV‐2
Author(s) -
CailletSaguy Célia,
Durbesson Fabien,
Rezelj Veronica V.,
Gogl Gergö,
Tran Quang Dinh,
Twizere JeanClaude,
Vignuzzi Marco,
Vincentelli Renaud,
Wolff Nicolas
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15881
Subject(s) - pdz domain , biology , coronavirus , virology , covid-19 , immune system , microbiology and biotechnology , computational biology , immunology , medicine , disease , pathology , infectious disease (medical specialty)
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 μ 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. 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.