D
IPR044322

Nonstructural protein 15, middle domain, alpha/betacoronavirus

InterPro entry
Short nameNSP15_M_alpha_beta_CoV
Overlapping
homologous
superfamilies
 
domain relationships

Description

The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded non structural proteins (NSP) plays a vital role during initial and intermediate phases of the viral life cycle. NSP15 forms a hexamer made of dimers of trimers which is suggested to be a functional unit, responsible for the endoribonuclease activity. The NSP15 monomer consists of three domains: N-terminal, middle and C-terminal
[7, 1]
. The catalytic function of NSP15 resides in the C-terminal NendoU domain. The active site carries six key residues conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, suggesting that its activity is important for sustained replication in the host
[4, 5]
.

This entry represents the non-catalytic middle domain of NSP15 from alpha and beta coronaviruses. This domain is formed by ten β-strands organised into three β-hairpins. It creates concave surfaces that may serve as interaction hubs with other proteins and RNA
[4, 6]
. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbours residues involved in hexamer formation and in trimer stability
[7, 3]
. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution
[2]
.

References

1.Cryo-EM structures of the SARS-CoV-2 endoribonuclease Nsp15 reveal insight into nuclease specificity and dynamics. Pillon MC, Frazier MN, Dillard LB, Williams JG, Kocaman S, Krahn JM, Perera L, Hayne CK, Gordon J, Stewart ZD, Sobhany M, Deterding LJ, Hsu AL, Dandey VP, Borgnia MJ, Stanley RE. Nat Commun 12, 636, (2021). PMID: 33504779

2.Insight into the evolution of nidovirus endoribonuclease based on the finding that nsp15 from porcine Deltacoronavirus functions as a dimer. Zheng A, Shi Y, Shen Z, Wang G, Shi J, Xiong Q, Fang L, Xiao S, Fu ZF, Peng G. J Biol Chem 293, 12054-12067, (2018). PMID: 29887523

3.Crystal structure of a monomeric form of severe acute respiratory syndrome coronavirus endonuclease nsp15 suggests a role for hexamerization as an allosteric switch. Joseph JS, Saikatendu KS, Subramanian V, Neuman BW, Buchmeier MJ, Stevens RC, Kuhn P. J. Virol. 81, 6700-8, (2007). View articlePMID: 17409150

4.An "Old" protein with a new story: Coronavirus endoribonuclease is important for evading host antiviral defenses. Deng X, Baker SC. Virology 517, 157-163, (2018). PMID: 29307596

5.Biochemical characterization of arterivirus nonstructural protein 11 reveals the nidovirus-wide conservation of a replicative endoribonuclease. Nedialkova DD, Ulferts R, van den Born E, Lauber C, Gorbalenya AE, Ziebuhr J, Snijder EJ. J. Virol. 83, 5671-82, (2009). PMID: 19297500

6.Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2. Kim Y, Jedrzejczak R, Maltseva NI, Wilamowski M, Endres M, Godzik A, Michalska K, Joachimiak A. Protein Sci. (2020). PMID: 32304108

7.New antiviral target revealed by the hexameric structure of mouse hepatitis virus nonstructural protein nsp15. Xu X, Zhai Y, Sun F, Lou Z, Su D, Xu Y, Zhang R, Joachimiak A, Zhang XC, Bartlam M, Rao Z. J. Virol. 80, 7909-17, (2006). View articlePMID: 16873248

Cross References

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