SARS-CoV-1 3a oligomerizes

Stable Identifier
Reaction [transition]
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

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

Cell Death Dis 2018
Event Information
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
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