D
IPR046443

NSP1, globular domain, alpha/betacoronavirus

InterPro entry
Short namea/bCoV_NSP1_glob
Overlapping
homologous
superfamilies
 
domain relationships

Description

This is the globular domain of NSP1 from alpha and betacoronavirus.

Nonstructural protein 1 (NSP1) is a critical virulence factor of coronaviruses (CoV) and plays key roles in suppressing host gene expression, which facilitates viral replication and immune evasion. NSP1 is a characteristic feature of alpha and betacoronavirus, which exhibits both functional conservation and mechanistic diversity in inhibiting host gene expression and antiviral responses
[1, 2, 4, 3]
. NSP1 binds to the 40S ribosomal subunit and inhibits host translation, and it also induces a template-dependent endonucleolytic cleavage of host mRNAs
[6, 8, 9, 11, 13]
, while viral mRNAs are less susceptible to NSP1-mediated inhibition of translation, because of their 5'-end leader sequence
[11, 12]
. NSP1 also suppresses the host innate immune functions by inhibiting type I interferon expression and host antiviral signalling pathways. The C-terminal domain binds to the mRNA entry tunnel interfering with mRNA binding (
IPR046442
)
[6, 7, 10]
. NSP1 consists of a globular domain arranged in a mixed parallel/antiparallel 6-stranded β-barrel with an α-helix covering one end of the barrel and another helix alongside the barrel
[5]
. In addition to the globular domain, bCoV NSP1s have a C-terminal domain
[1, 2, 3]
.

References

1.Structure of alphacoronavirus transmissible gastroenteritis virus nsp1 has implications for coronavirus nsp1 function and evolution. Jansson AM. J. Virol. 87, 2949-55, (2013). View articlePMID: 23269811

2.Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1. Shen Z, Ye G, Deng F, Wang G, Cui M, Fang L, Xiao S, Fu ZF, Peng G. J Virol 92, e01896-17, (2018). PMID: 29237834

3.Structural characterization of nonstructural protein 1 from SARS-CoV-2. Semper C, Watanabe N, Savchenko A. iScience 24, 101903, (2021). PMID: 33319167

4.A conserved region of nonstructural protein 1 from alphacoronaviruses inhibits host gene expression and is critical for viral virulence. Shen Z, Wang G, Yang Y, Shi J, Fang L, Li F, Xiao S, Fu ZF, Peng G. J Biol Chem 294, 13606-13618, (2019). PMID: 31350335

5.Novel beta-barrel fold in the nuclear magnetic resonance structure of the replicase nonstructural protein 1 from the severe acute respiratory syndrome coronavirus. Almeida MS, Johnson MA, Herrmann T, Geralt M, Wuthrich K. J. Virol. 81, 3151-61, (2007). View articlePMID: 17202208

6.Severe acute respiratory syndrome coronavirus protein nsp1 is a novel eukaryotic translation inhibitor that represses multiple steps of translation initiation. Lokugamage KG, Narayanan K, Huang C, Makino S. J. Virol. 86, 13598-608, (2012). PMID: 23035226

7.Coronavirus nonstructural protein 1: Common and distinct functions in the regulation of host and viral gene expression. Narayanan K, Ramirez SI, Lokugamage KG, Makino S. Virus Res. 202, 89-100, (2015). PMID: 25432065

8.SARS coronavirus nsp1 protein induces template-dependent endonucleolytic cleavage of mRNAs: viral mRNAs are resistant to nsp1-induced RNA cleavage. Huang C, Lokugamage KG, Rozovics JM, Narayanan K, Semler BL, Makino S. PLoS Pathog. 7, e1002433, (2011). PMID: 22174690

9.A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein. Kamitani W, Huang C, Narayanan K, Lokugamage KG, Makino S. Nat. Struct. Mol. Biol. 16, 1134-40, (2009). PMID: 19838190

10.Evasion of Type I Interferon by SARS-CoV-2. Xia H, Cao Z, Xie X, Zhang X, Chen JY, Wang H, Menachery VD, Rajsbaum R, Shi PY. Cell Rep 33, 108234, (2020). PMID: 32979938

11.SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation. Schubert K, Karousis ED, Jomaa A, Scaiola A, Echeverria B, Gurzeler LA, Leibundgut M, Thiel V, Muhlemann O, Ban N. Nat Struct Mol Biol 27, 959-966, (2020). PMID: 32908316

12.SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses. Banerjee AK, Blanco MR, Bruce EA, Honson DD, Chen LM, Chow A, Bhat P, Ollikainen N, Quinodoz SA, Loney C, Thai J, Miller ZD, Lin AE, Schmidt MM, Stewart DG, Goldfarb D, De Lorenzo G, Rihn SJ, Voorhees RM, Botten JW, Majumdar D, Guttman M. Cell 183, 1325-1339.e21, (2020). PMID: 33080218

13.Dynamic competition between SARS-CoV-2 NSP1 and mRNA on the human ribosome inhibits translation initiation. Lapointe CP, Grosely R, Johnson AG, Wang J, Fernandez IS, Puglisi JD. Proc Natl Acad Sci U S A 118, (2021). PMID: 33479166

Cross References

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