NSP4 (rotavirus)

The rotavirus nonstructural protein NSP4 was the first viral enterotoxin discovered.^[1] It is a viroporin^[2] and induces diarrhea and causes Ca²⁺-dependent transepithelial secretion.^[3]

NSP4 (rotavirus)
Identifiers
Symbol	Rota_NSP4
Pfam	PF01452
InterPro	IPR002107
CATH	1g1iA00
SCOP2	1g1i / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

A transmembrane glycoprotein, NSP4 is organized into three main domains: a three-helical TM domain in the N-terminus (also a viroporin domain), a central cytoplasmic coiled-coil domain for multimerization, and a C-terminal flexible region. It can also be secreted out of the cell. As of 2019, only structures of the central domain, which is responsible for diarrhea, has been solved. It oligomerizes into dimeric, tetrameric, pentameric, and even higher-order forms.^[4]

References

1. Dong Y, Zeng CQ, Ball JM, Estes MK, Morris AP (April 1997). "The rotavirus enterotoxin NSP4 mobilizes intracellular calcium in human intestinal cells by stimulating phospholipase C-mediated inositol 1,4,5-trisphosphate production". Proceedings of the National Academy of Sciences of the United States of America. 94 (8): 3960–5. Bibcode:1997PNAS...94.3960D. doi:10.1073/pnas.94.8.3960. PMC 20550. PMID 9108087.
2. Pham T, Perry JL, Dosey TL, Delcour AH, Hyser JM (March 2017). "The Rotavirus NSP4 Viroporin Domain is a Calcium-conducting Ion Channel". Scientific Reports. 7: 43487. Bibcode:2017NatSR...743487P. doi:10.1038/srep43487. PMC 5335360. PMID 28256607.
3. Gebert JT, Hyser J (May 2022). "Using Forward and Reverse Genetics to Understand Calcium Dysregulation in Enteric Viral Virulence". FASEB Journal. 36 (Suppl 1). doi:10.1096/fasebj.2022.36.S1.R3214. PMID 35557094. S2CID 248633853.
4. Hu L, Crawford SE, Hyser JM, Estes MK, Prasad BV (August 2012). "Rotavirus non-structural proteins: structure and function". Current Opinion in Virology. 2 (4): 380–8. doi:10.1016/j.coviro.2012.06.003. PMC 3422752. PMID 22789743.