H
IPR037230

Non-structural protein NSP8 superfamily, coronavirus

InterPro entry
Short nameNSP8_sf_CoV
Overlapping entries
 

Description

Viral non-structural protein NSP8 is part of the RNA-dependent RNA polymerase (RdRp) complex and forms a heterotetramer consisting of one molecule of NSP7, two copies of NSP8 and one of NSP12
[1]
. NSP8 and NSP7 adopts a hollow cylinder-like structure
[4, 8]
in which the dimensions of the central channel and positive electrostatic properties of the cylinder imply that it confers processivity on RdRp
[4, 1]
. NSP7 and NSP8 are co-factors for the catalytic NSP12 that play a role in the stabilisation of NSP12 regions involved in RNA binding and are essential for a highly active NSP12 polymerase complex
[5]
. It has been demonstrated that NSP8 from human coronavirus 229E acts as an oligo(U)-templated polyadenylyltransferase but also has robust (mono/oligo) adenylate transferase activities
[6]
. NSP8 has N-terminal and C-terminal D/ExD/E conserved motifs. The N-terminal motif is critical for RNA polymerase activity as these residues are part of the Mg2-binding active site
[7]
. NSP8 has a 'golf club'-like structure composed of a long α-helix N-terminal 'shaft' subdomain and an α/β C-terminal 'head' subdomain consisting of three α-helices and seven β-strands (
2AHM
). The seven β-strands form an open-barrel with two antiparallel β-sheets packed orthogonally. More than half the residues in the C-terminal domain are hydrophobic, and the whole domain forms a tight hydrophobic core
[4, 2, 3]
.

Together with NSP9, NSP8 suppresses protein integration into the cell membrane, thus, disrupting host immune defenses
[9]
.

The core structure of NSP8 has an α-β(2)-α-β(4)-α-β fold with bifurcated barrel-like β-sheet.

References

1.Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first 6 months of the COVID-19 pandemic. Lubin JH, Zardecki C, Dolan EM, Lu C, Shen Z, Dutta S, Westbrook JD, Hudson BP, Goodsell DS, Williams JK, Voigt M, Sarma V, Xie L, Venkatachalam T, Arnold S, Alfaro Alvarado LH, Catalfano K, Khan A, McCarthy E, Staggers S, Tinsley B, Trudeau A, Singh J, Whitmore L, Zheng H, Benedek M, Currier J, Dresel M, Duvvuru A, Dyszel B, Fingar E, Hennen EM, Kirsch M, Khan AA, Labrie-Cleary C, Laporte S, Lenkeit E, Martin K, Orellana M, Ortiz-Alvarez de la Campa M, Paredes I, Wheeler B, Rupert A, Sam A, See K, Soto Zapata S, Craig PA, Hall BL, Jiang J, Koeppe JR, Mills SA, Pikaart MJ, Roberts R, Bromberg Y, Hoyer JS, Duffy S, Tischfield J, Ruiz FX, Arnold E, Baum J, Sandberg J, Brannigan G, Khare SD, Burley SK. Proteins (2021). PMID: 34580920

2.NMR Structure of the SARS-CoV Nonstructural Protein 7 in Solution at pH 6.5. Johnson MA, Jaudzems K, Wuthrich K. J Mol Biol 402, 619-28, (2010). PMID: 20709084

3.A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus. Imbert I, Guillemot JC, Bourhis JM, Bussetta C, Coutard B, Egloff MP, Ferron F, Gorbalenya AE, Canard B. EMBO J 25, 4933-42, (2006). PMID: 17024178

4.Insights into SARS-CoV transcription and replication from the structure of the nsp7-nsp8 hexadecamer. Zhai Y, Sun F, Li X, Pang H, Xu X, Bartlam M, Rao Z. Nat. Struct. Mol. Biol. 12, 980-6, (2005). View articlePMID: 16228002

5.Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Kirchdoerfer RN, Ward AB. Nat Commun 10, 2342, (2019). PMID: 31138817

6.Identification and Characterization of a Human Coronavirus 229E Nonstructural Protein 8-Associated RNA 3'-Terminal Adenylyltransferase Activity. Tvarogova J, Madhugiri R, Bylapudi G, Ferguson LJ, Karl N, Ziebuhr J. J. Virol. 93, (2019). PMID: 30918070

7.The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension. te Velthuis AJ, van den Worm SH, Snijder EJ. Nucleic Acids Res. 40, 1737-47, (2012). PMID: 22039154

8.Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase. Wang Q, Wu J, Wang H, Gao Y, Liu Q, Mu A, Ji W, Yan L, Zhu Y, Zhu C, Fang X, Yang X, Huang Y, Gao H, Liu F, Ge J, Sun Q, Yang X, Xu W, Liu Z, Yang H, Lou Z, Jiang B, Guddat LW, Gong P, Rao Z. Cell 182, 417-428.e13, (2020). PMID: 32526208

9.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

GO terms

Cross References

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