PROSITE documentation PDOC52074Coronavirus Nsp4 ectodomain (4Ecto) profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC52074
Coronaviruses (CoVs) 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 [E1].
The CoV replicase gene encodes two overlapping polyproteins, termed pp1a and pp1ab, which mediate viral replication and transcription. The polypeptides pp1a and pp1ab are processed by the action of a main protease (Nsp5) (see <PDOC51442>) and of one or two papain-like proteases (PLpro) (see <PDOC51124>) found in Nsp3 into non-structural proteins (Nsps) to form the replication/ transcription complex (RTC). Among them, the replicase proteins Nsp3, Nsp4, and Nsp6 contain transmembrane (TM)-spanning sequences that are important for sequestering endoplasmic reticulum (ER) membranes to form the double-membrane vesicles (DMVs) which are the site of viral RNA synthesis. Nsp3 and Nsp4 are the minimal viral components required to induce DMV formation and to form a double-membrane-spanning pore, essential for the transport of newly synthesized viral RNAs. The Nsp3-Nsp4 pore complex comprises 12 copies each of Nsp3 and Nsp4, organized in 4 concentric stacking hexamer rings, mimicking a miniature nuclear pore complex (see <PDB:8YAX>). Nsp4 contains six TMHs with its ectodomain (4Ecto) localized in the intermembrane space and its carboxy-terminal domain (CTD) in the DMV lumen, forming two layers of concentric stacking hexamers constituting the lower base of the pore complex. The 3Ecto domain (see <PDOC51993>) attaches to the upper surface of the 4Ecto domain, which is mediated by a combination of hydrophobic and hydrophilic interactions [1,2,3].
The profile we developed covers the entire CoV 4Ecto domain.
Last update:August 2025 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Zimmermann L. Zhao X. Makroczyova J. Wachsmuth-Melm M. Prasad V. Hensel Z. Bartenschlager R. Chlanda P. |
| Title | SARS-CoV-2 nsp3 and nsp4 are minimal constituents of a pore spanning replication organelle. | |
| Source | Nat. Commun. 14:7894-7894(2023). | |
| PubMed ID | 38036567 | |
| DOI | 10.1038/s41467-023-43666-5 |
| 2 | Authors | Huang Y. Wang T. Zhong L. Zhang W. Zhang Y. Yu X. Yuan S. Ni T. |
| Title | Molecular architecture of coronavirus double-membrane vesicle pore complex. | |
| Source | Nature 633:224-231(2024). | |
| PubMed ID | 39143215 | |
| DOI | 10.1038/s41586-024-07817-y |
| 3 | Authors | Chen A. Lupan A.M. Quek R.T. Stanciu S.G. Asaftei M. Stanciu G.A. Hardy K.S. de Almeida Magalhaes T. Silver P.A. Mitchison T.J. Salic A. |
| Title | A coronaviral pore-replicase complex links RNA synthesis and export from double-membrane vesicles. | |
| Source | Sci. Adv. 10:Eadq9580-Eadq9580(2024). | |
| PubMed ID | 39514670 | |
| DOI | 10.1126/sciadv.adq9580 |
| E1 | Title | https://viralzone.expasy.org/30?outline=all_by_species |
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