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

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

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

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

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
Authored
Stephan, R  (2021-05-07)
Reviewed
D'Eustachio, P  (2021-01-26)
Created
Stephan, R  (2021-05-12)
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