SARS-CoV-2 E pentamer binds TJP1

Stable Identifier
R-HSA-9754644
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
endoplasmic reticulum-Golgi intermediate compartment membrane, cytosol
ReviewStatus
5/5
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SARS-CoV-2 E pentamer binds TJP1
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Tight junction protein ZO-1 (TJP1, also known as zonula occludens-1) acts a scaffolding protein that regulates the formation of tight junction complexes. TJP1 scaffolding function is crucial for the establishment and maintenance of epithelial polarity and barrier formation in mammals. TJP1 has three PSD-95/Dlg/ZO-1 (PDZ) domains that promote multiple protein-protein interactions. A functional PDZ domain-binding motif has been identified at the carboxy-terminus end of SARS-CoV-2 E (Caillet-Saguy C et al. 2021; Chai J et al. 2021; Shepley-McTaggart A et al. 2021). NMR spectroscopy identified the pentameric structure of transmembrane domain of SARS‐CoV‐2 E protein in lipid bilayers (Mandala VS et al. 2020). Glutathione S-transferase (GST)-fusion protein technique and homogeneous time resolve fluorescence showed that the SARS-CoV-2 E protein interacts with PDZ domain # 2 of TJP1 (Shepley-McTaggart A et al. 2021). A high‐throughput approach of affinity‐profiling against the full human PDZome identified TJP1 and other human PDZ-containing proteins as interactors of SARS-CoV-2 E (Caillet-Saguy C et al. 2021). Further, SARS-CoV-2 infection was found to distort the TJP1 expression causing barrier dysfunction in vitro-cultured polarized human airway epithelium (Hao S et al. 2020). TJP1 knockdown by siRNA transfection in human lung A549 cells slightly increased SARS‐CoV‐2 replication (Caillet-Saguy C et al. 2021). These findings suggest that SARS-CoV-2 infection targets PDZ-containing TJP1 that is recognized by the viral E protein.

This Reactome event describes interaction between human TJP1 and SARS-CoV-2 E at the ER-Golgi intermediate compartment (ERGIC) where E localizes for viral assembly and budding. However, additional studies are needed to verify this interaction at ERGIC in vivo experiments.


Literature References
PubMed ID Title Journal Year
34106957 SARS-CoV-2 Envelope (E) protein interacts with PDZ-domain-2 of host tight junction protein ZO1

Harty, RN, Mullin, JM, Cassel, J, Oliva, I, DiGuilio, K, Rybakovsky, E, Bedford, MT, Shepley-McTaggart, A, Sudol, M, Sagum, CA, Liang, J

PLoS One 2021
33864728 Host PDZ-containing proteins targeted by SARS-CoV-2

Rezelj, VV, Vincentelli, R, Twizere, JC, Vignuzzi, M, Caillet-Saguy, C, Tran, QD, Durbesson, F, Gogl, G, Wolff, N

FEBS J 2021
Participants
Input
Output
Participates
as an event of
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Authored
Shamovsky, V  (2021-10-27)
Reviewed
Messina, F  (2022-02-18)
Created
Shamovsky, V  (2021-09-30)
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