PROSITE documentation PDOC51919Sarbecovirus X4e domain profile
Coronaviruses are enveloped positive-strand RNA viruses that infect many species, including humans, other mammals, and birds. After infection, the host may develop respiratory, bowel, liver, and neurological diseases. Coronaviruses are divided into four genera: αcoronavirus, βcoronavirus, γcoronavirus, and Deltacoronavirus. SARS, SARS-CoV-2, BatCoV RaTG13 and Bat-SARS-like coronavirus (BATSL-CoVZXC21 and BAT-SL-CoVZC45) belong to the Sarbecovirus subgenus of βcoronavirus [1,2,3,E1].
Coronaviruses code for the characteristic proteins replicase polyprotein (pp1ab), spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins. In addition, Sarbecoviruses code for subgroup-specific accessory proteins that are thought to be dispensable for viral replication in cell culture, but may be important for virus-host interactions and thus contribute to the virus' fitness [1].
The Sarbecovirus accessory protein X4, also called 7a or U122, is likely to be a type I membrane protein, with the amino-terminal hydrophilic domain oriented inside the lumen of the ER/Golgi or on the surface of the cell membrane or virus particle, depending on the localization of the protein. It has been suggested that X4e contains a binding site for the α(L) integrin subunit I-domain of LFA-1 [1,2].
The X4 ectodomain (X4e) forms a well defined β-sandwich fold (see <PDB:1YO4>). It is built up from seven β-strands so that four strands form one β-sheet and three strands form a second sheet. The sheets are closely packed or 'sandwiched' against each other. Each sheet is amphipathic with the hydrophobic side facing inward. The larger four-stranded β-sheet consists of strands A, G, F, and C, the smaller three-stranded β-sheet consists of strands B, E, and D. The overall appearance of the seven stranded β-sandwich fold of the X4e domain very much reminds one to an immunoglobulin (Ig) like fold, that shows some features resembling those of the Dl domain of ICAM-1. All β-strands align in anti-parallel fashion, as it is well-known for most immunoglobulin-like domains, with the exception of strand A, which aligns parallel to strand G. Two disulfide bonds link both sheets on opposite edges therefore stabilizing the β-sandwich structure. The first disulfide of X4e connects the end of strand A to the E-F loop, while the second disulfide connects the short B-C and F-G loops [1,2].
The profile we developed covers the entire X4e domain.
Last update:March 2020 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Haenel K. Stangler T. Stoldt M. Willbold D. |
| Title | Solution structure of the X4 protein coded by the SARS related coronavirus reveals an immunoglobulin like fold and suggests a binding activity to integrin I domains. | |
| Source | J. Biomed. Sci. 13:281-293(2006). | |
| PubMed ID | 16328780 | |
| DOI | 10.1007/s11373-005-9043-9 |
| 2 | Authors | Nelson C.A. Pekosz A. Lee C.A. Diamond M.S. Fremont D.H. |
| Title | Structure and intracellular targeting of the SARS-coronavirus Orf7a accessory protein. | |
| Source | Structure 13:75-85(2005). | |
| PubMed ID | 15642263 | |
| DOI | 10.1016/j.str.2004.10.010 |
| 3 | Authors | Fahmi M. Kubota Y. Ito M. |
| Title | Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV. | |
| Source | Infect. Genet. Evol. 81:104272-104272(2020). | |
| PubMed ID | 32142938 | |
| DOI | 10.1016/j.meegid.2020.104272 |
| E1 | Title | https://viralzone.expasy.org/30?outline=all_by_species |
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