SARS-CoV-1 3a tetramerizes

Stable Identifier
R-HSA-9731012
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human SARS coronavirus
Compartment
plasma membrane
ReviewStatus
5/5
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SARS-CoV-1 3a tetramerizes
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SARS-CoV-1 viroporin 3a is a membrane-bound protein that translocates to the plasma membrane and, via shedding, to other cells. It forms a homotetrameric inward-rectifying potassium ion channel by itself, causing apoptotic or necrotic cell death (Lu et al. 2006; Chan CM et al. 2009; Yue Y et al, 2018). The cysteine-rich domain of 3a is involved in the formation of dimers and tetramers to generate the ion channel (Lu et al. 2006; Chan CM et al. 2009). Moreover, Cys133 is required for the 3a oligomerization (Lu et al. 2006). Structural studies of ion channels formed in lipid nanodiscs by SARS-CoV-2 3a, an ortholog of SARS-CoV-1 3a, confirm the formation of homo-dimers and -tetramers (Kern DM et al. 2020). The oligomerization process is greatly enhanced when receptor-interacting serine/threonine-protein kinase 3 (RIPK3) binds to 3a monomers (Yue et al, 2018). The RIPK3 oligomerization ability does not depend on its kinase activity, as a dead form induced necrotic cell death to a similar extent as WT RIPK3 when co-expressed with SARS-Cov-1 3a in human embryonic kidney 293T cells (Yue Y et al, 2018).
Literature References
PubMed ID Title Journal Year
23483519 Assembling an ion channel: ORF 3a from SARS-CoV

Chien, TH, Chiang, YL, Chen, CP, Henklein, P, Hänel, K, Hwang, IS, Willbold, D, Fischer, WB

Biopolymers 2013
30185776 SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death

Yue, Y, Nabar, NR, Shi, CS, Kamenyeva, O, Xiao, X, Hwang, IY, Wang, M, Kehrl, JH

Cell Death Dis 2018
Participants
Input
Output
Participates
as an event of
This event is regulated
Positively by
Regulator
RIPK3:O-glycosyl 3a [plasma membrane] (Homo sapiens)
Disease
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
Cross References
Mondo
Authored
Stephan, R  (2021-05-07)
Reviewed
D'Eustachio, P  (2021-01-26)
Created
Stephan, R  (2021-05-12)
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