SARS-CoV-1 3a oligomerizes

Stable Identifier
R-HSA-9686336
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Human SARS coronavirus
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Receptor interacting serine/threonine protein kinase 3 (RIPK3) was found to induce oligomerization of severe acute respiratory syndrome-associated coronavirus type 1 (SARS-CoV-1) 3a (studied with the oligomerization-deficient viral 3a-flag C133A mutant) in human embryonic kidney 293 (HEK293) that do not express endogenous RIPK3 or MLKL, after co-transfection of viral 3a and RIPK3 (Yue Y et al. 2018). RIPK3-induced oligomerization of viral 3a helped drive necrotic cell death in RIPK3-expressing HEK293 and 5-Aza-2′-deoxycytidine (5-AD)-treated human alveolar epithelial A549 cells (Yue Y et al. 2018). The A549 cell line is resistant to the traditional necroptotic stimuli, but treatment with hypomethylating agents such as 5-AD induced RIPK3 expression (Yue Y et al. 2018). The results of the study suggest that SARS-Cov-1 3a does not induce cell death in the absence of RIPK3, but induces significant oligomerization-dependent death in the presence of endogenous RIPK3. (Yue Y et al. 2018). RIPK3 kinase activity was dispensable for the RIPK3-driven oligomerization of 3a (Yue Y et al. 2018). Further, a disulfide bond formation at cysteine-133 was found to mediate the oligomerization of 3a (Lu W et al. 2006) and the addition of DTT to cell lysates from HEK293 cells after co-transfection of viral 3a and RIPK3 completely erased the oligomerization 3a, confirming its disulfide bond dependence (Yue Y et al. 2018). SARS-CoV-1 3a formed homodimer and homotetramer complexes in 3a-cDNA-transfected HEK 293 cells (Lu W et al. 2006). The tetrameric pattern is a very common feature of a protein involved in ion channel formation (Shi N et al. 2006).

Literature References
PubMed ID Title Journal Year
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
Participates
Event Information
Disease
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
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