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O R F 9 b
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F r o m W i k i p e d i a , t h e f r e e e n c y c l o p e d i a
ORF9b (formerly sometimes called ORF13 ) is a gene that encodes a viral accessory protein in coronaviruses of the subgenus Sarbecovirus , including SARS-CoV and SARS-CoV-2 . It is an overlapping gene whose open reading frame is entirely contained within the N gene, which encodes coronavirus nucleocapsid protein .[2] [3] [4] The encoded protein is 97 amino acid residues long in SARS-CoV[2] [3] and 98 in SARS-CoV-2,[4] in both cases forming a protein dimer .
Nomenclature [ edit ]
There has been inconsistency in the nomenclature used for this gene in the scientific literature. In some work on SARS-CoV, it has been referred to as ORF13. It has also sometimes been referred to as ORF9a, resulting in a downstream ORF of 76 codons in SARS-CoV, also overlapping with the N gene , being designated ORF9b. The recommended nomenclature refers to the longer ORF as 9b and the downstream, shorter ORF as ORF9c .[5]
Structure [ edit ]
The ORF9b protein is 97 amino acid residues long in SARS-CoV[2] [3] and 98 in SARS-CoV-2.[4] It forms a beta sheet -rich homodimer with a hydrophobic cavity in the center that binds lipids .[2] [3] [4] The lipid-binding cavity may serve as an unusual mechanism for anchoring the protein to membranes.[1]
A fragment of the SARS-CoV-2 ORF9b protein has been structurally characterized in a protein complex with Tom70 in which ORF9b forms an alpha helix rather than the beta-sheet structure observed in isolation.[6] This fold switching behavior is also consistent with bioinformatics predictions and may also occur for the SARS-CoV homolog.[7]
Expression and localization [ edit ]
ORF9b is one of two overlapping genes fully contained within the open reading frame of the N gene encoding coronavirus nucleocapsid protein , the other being ORF9c . ORF9b is expressed by ribosome leaky scanning from its bicistronic subgenomic RNA .[2] [3] [8] Unlike its neighbor ORF9c, its length is well conserved in sarbecoviruses and there is strong evidence it is a functional protein-coding gene .[9]
In SARS-CoV, the protein is localized to the endoplasmic reticulum (ER )[3] and to intracellular vesicles .[2] [1] It does not have a nuclear localization sequence but can enter the cell nucleus by passive diffusion ; it does however have a nuclear export sequence for exit from the nucleus.[2] [3] In SARS-CoV-2, it is reportedly associated with the mitochondrial membrane.[4]
Function [ edit ]
The function of the ORF9b protein is not well characterized. It is not essential for viral replication .[2]
Viral protein interactions [ edit ]
The ORF9b protein has been reported to interact with a number of other viral proteins, including ORF6 , non-structural protein 5 , non-structural protein 14 , and coronavirus envelope protein .[2] It has been detected in mature SARS-CoV virions and thus may be a minor viral structural protein .[2] [3] [8]
Host cell effects [ edit ]
The ORF9b protein may be involved in modulating the host's immune system response. The SARS-CoV-2 protein has been reported to suppress interferon response via its interactions with Tom70 , a component of the mitochondrial translocase of the outer membrane (TOM) complex.[6] [10]
References [ edit ]
^ a b c d e f g h i j Liu DX, Fung TS, Chong KK, Shukla A, Hilgenfeld R (September 2014). "Accessory proteins of SARS-CoV and other coronaviruses" . Antiviral Research . 109 : 97–109. doi :10.1016/j.antiviral.2014.06.013 . PMC 7113789 . PMID 24995382 .
^ a b c d e f g h McBride R, Fielding BC (November 2012). "The role of severe acute respiratory syndrome (SARS)-coronavirus accessory proteins in virus pathogenesis" . Viruses . 4 (11 ): 2902–2923. doi :10.3390/v4112902 . PMC 3509677 . PMID 23202509 .
^ a b c d e Redondo N, Zaldívar-López S, Garrido JJ, Montoya M (7 July 2021). "SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns" . Frontiers in Immunology . 12 : 708264. doi :10.3389/fimmu.2021.708264 . PMC 8293742 . PMID 34305949 .
^ Jungreis I, Nelson CW, Ardern Z, Finkel Y, Krogan NJ, Sato K, et al. (June 2021). "Conflicting and ambiguous names of overlapping ORFs in the SARS-CoV-2 genome: A homology-based resolution" . Virology . 558 : 145–151. doi :10.1016/j.virol.2021.02.013 . PMC 7967279 . PMID 33774510 .
^ a b Gao X, Zhu K, Qin B, Olieric V, Wang M, Cui S (May 2021). "Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions" . Nature Communications . 12 (1 ): 2843. Bibcode :2021NatCo..12.2843G . doi :10.1038/s41467-021-23118-8 . PMC 8121815 . PMID 33990585 .
^ Porter LL (August 2021). "Predictable fold switching by the SARS-CoV-2 protein ORF9b" . Protein Science . 30 (8 ): 1723–1729. doi :10.1002/pro.4097 . PMC 8242659 . PMID 33934422 .
^ a b Xu K, Zheng BJ, Zeng R, Lu W, Lin YP, Xue L, et al. (June 2009). "Severe acute respiratory syndrome coronavirus accessory protein 9b is a virion-associated protein" . Virology . 388 (2 ): 279–285. doi :10.1016/j.virol.2009.03.032 . PMC 7103405 . PMID 19394665 .
^ Jungreis I, Sealfon R, Kellis M (May 2021). "SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes" . Nature Communications . 12 (1 ): 2642. Bibcode :2021NatCo..12.2642J . doi :10.1038/s41467-021-22905-7 . PMC 8113528 . PMID 33976134 .
^ Jiang HW, Zhang HN, Meng QF, Xie J, Li Y, Chen H, et al. (September 2020). "SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70" . Cellular & Molecular Immunology . 17 (9 ): 998–1000. doi :10.1038/s41423-020-0514-8 . PMC 7387808 . PMID 32728199 .
R e t r i e v e d f r o m " https://en.wikipedia.org/w/index.php?title=ORF9b&oldid=1221010079 "
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