nsp15 forms a hexamer

Stable Identifier
Reaction [binding]
Homo sapiens
Related Species
Human SARS coronavirus
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nsp15 forms a hexamer. Hexamer formation is necessary for the endonuclease activity of nsp15. nsp15 preferentially cleaves 3' of uridines, generating 2'-3' cyclic phosphates after cleavage. nsp15 requires Mn2+ ions for catalytic activity. C-terminal domain contains the active site, which faces away from the center of the hexamer and contains the extreme C-terminal residues. The middle and the N-terminal domains form extensive contacts with the other subunits of the hexamer. While the hexamer is likely formed by two asymmetric trimers, a trimer is not a stable intermediate. The catalytic pocket of nsp15 resembles the catalytic pocket of RNase A and their mechanism of endoribonuclease action is likely the same. Functional nsp15 is needed for production of viable virions. nsp15 is a genetic marker of the order Nidovirales, which includes the family Coronaviridae, as it is not present in other RNA viruses (Guarino et al. 2005, Ricagno et al. 2006, Bhardwaj et al. 2006, Joseph et al. 2007, Bhardwaj et al. 2008, Bhardwaj et al. 2012).

Literature References
PubMed ID Title Journal Year
17409150 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. 2007
16216269 Mutational analysis of the SARS virus Nsp15 endoribonuclease: identification of residues affecting hexamer formation

Guarino, LA, Bhardwaj, K, Dong, W, Sun, J, Holzenburg, A, Kao, C

J. Mol. Biol. 2005
16828802 RNA recognition and cleavage by the SARS coronavirus endoribonuclease

Bhardwaj, K, Sun, J, Holzenburg, A, Guarino, LA, Kao, CC

J. Mol. Biol. 2006
22301153 The coronavirus endoribonuclease Nsp15 interacts with retinoblastoma tumor suppressor protein

Bhardwaj, K, Liu, P, Leibowitz, JL, Kao, CC

J. Virol. 2012
16882730 Crystal structure and mechanistic determinants of SARS coronavirus nonstructural protein 15 define an endoribonuclease family

Ricagno, S, Egloff, MP, Ulferts, R, Coutard, B, Nurizzo, D, Campanacci, V, Cambillau, C, Ziebuhr, J, Canard, B

Proc. Natl. Acad. Sci. U.S.A. 2006
18045871 Structural and functional analyses of the severe acute respiratory syndrome coronavirus endoribonuclease Nsp15

Bhardwaj, K, Palaninathan, S, Alcantara, JM, Yi, LL, Guarino, L, Sacchettini, JC, Kao, CC

J. Biol. Chem. 2008
Participant Of
Name Identifier Synonyms
severe acute respiratory syndrome 2945 SARS-CoV infection, SARS
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