accessory protein ORF3a of severe acute respiratory syndrome-associated coronavirus and similar proteins from related betacoronavirus
This model represents the accessory protein ORF3a of Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV), SARS-COV-2 (also called 2019 novel coronavirus or 2019-nCoV), and related betacoronaviruses in the Sarbecovirus subgenus (B lineage). There are five essential genes in CoVs that result in the following gene products: Spike (S) protein, Membrane (M) glycoprotein, Nucleocapsid (N), Envelope (E) protein, and replicase/protease polyproteins (ORF1ab); all are required to produce a structurally complete viral particle. In addition, CoV genomes also contain ORFs coding for accessory proteins that are specific for certain CoV lineages or for a particular CoV. In general, CoV accessory proteins are considered to be dispensable for viral replication; however, several accessory proteins have been shown to exhibit functions in virus-host interactions during CoV infection. SARS-CoV mRNA 3 encodes the distinct proteins ORF3a and ORF3b, which are translated in different reading frames. Accessory protein ORF3a, also called protein 3a and protein X1, is the largest ORF protein in SARS-CoV. It is also called accessory protein 3 or protein 3 in some bat coronaviruses. SARS-CoV ORF3a promotes membrane rearrangement and cell death; it induces vesicle formation and is necessary for SARS-CoV-induced Golgi fragmentation. It has also been found to activate NF-kappaB and the NLRP3 inflammasome by promoting TNF receptor-associated factor 3 (TRAF3)-dependent ubiquitination of p105 and ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain). The cytoplasmic domain of SARS-CoV ORF3a, composed of amino acids at the C-terminal region, has sequence similarity to a calcium pump present in Plasmodium falciparum and has been shown to bind calcium in vitro. SARS-CoV-2 3a is able to form ion channels; it is a Class IIIA viroporin, having 3 transmembrane helices per protomer and a lumenal amino terminus and cytosolic carboxyl terminus. It can form dimers, tetramers, and potentially higher order oligomers. It has been shown to form cation channels with modest selectivity for Ca2+ and K+ over Na+.
Structure:6XDC: SARS-CoV-2 3a ion channel in a closed/inactive state, dimer interface; contacts at 4A
Comment:the SARS-CoV-2 3a ion channel (viroporin) is classified as Class IIIA: it has 3 transmembrane helices per protomer and a lumenal amino terminus and cytosolic carboxyl terminus
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