SARS-CoV-1 3a tetramer induces potassium efflux

Stable Identifier
R-HSA-9731072
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Human SARS coronavirus
Compartment
ReviewStatus
5/5
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This Reactome event shows the SARS‑CoV‑1 viroporin 3a‑triggered potassium (K+) efflux across the plasma membrane.

SARS-CoV-1 viroporin 3a is a membrane protein that can translocate to the plasma membrane and, via shedding, to other cells. The cytoplasmic domain of 3a contains the tyrosine based sorting motif (YXXΦ, where X can be any residue and Φ is a residue with a bulky hydrophobic side chain) which is responsible for Golgi to plasma membrane transport (Minakshi R & Padhan K 2014). In the membranes, 3a forms a homotetrameric inward-rectifying potassium ion channel which is inhibited by barium ions and 4-aminopyridine (Chan CM et al. 2009; Chien TH et al. 2013). The ion channel activity of 3a is linked to SARS-CoV-1-induced cell death in various mammalian cells (Law PTW et al. 2005; Freundt EC et al. 2010; Chan CM et al. 2009; Chien TH et al. 2013; Chen IY et al. 2019; Yue Y et al. 2018). Blocking potassium efflux from the cell impaired the ability of viral 3a protein to induce the caspase-dependent extrinsic apoptotic signalling pathway (Chan CM et al, 2009; Chien TH et al, 2013). In addition, membrane-bound 3a oligomers were found to activate the NLRP3 inflammasome and interleukin 1 beta (IL-1β) secretion via potassium efflux causing necrotic cell death (Chen IY et al. 2019; Yue Y et al. 2018). These data suggest that the ion channel activity of SARS-CoV-1 3a oligomers regulates both non-lytic apoptosis and highly inflammatory pyroptosis.Further, mutagenesis studies revealed that membrane association (Ren Y et al. 2020) and ion channel activities (Yue Y et al. 2018) of SARS-CoV-1 3a are involved but not critical for triggering cell death suggesting that 3a can also induce apoptotic or pyroptotic cell death in a membrane-independent manner (Ren Y et al. 2020).

Literature References
PubMed ID Title Journal Year
19398035 The ion channel activity of the SARS-coronavirus 3a protein is linked to its pro-apoptotic function

Zhai, S, Tsoi, H, Tsui, SK, Yao, X, Chan, CM, Wong, CO, Chan, WM, Chan, WY, Chan, HY

Int. J. Biochem. Cell Biol. 2009
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
Participants
Input
Participates
Catalyst Activity

inward rectifier potassium channel activity of O-glycosyl 3a tetramer [plasma membrane]

Disease
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
Cross References
Rhea
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Reviewed
Created
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