nsp16 binds nsp10

Stable Identifier
R-HSA-9683429
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human SARS coronavirus
Compartment
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The non-structural protein 16 (nsp16) of the human SARS coronavirus is an AdoMet-dependent (nucleoside-2'O)-methyltransferase involved in capping of viral RNAs. nsp16 binds to nsp10, which serves as a cofactor for nsp16 (Bouvet et al. 2010, Lugari et al. 2010). Nsp16 alone is unstable and exhibits 2'-O-methyltransferase activity only in complex with nsp10 (Debarnot et al, 2011; Decroly et al, 2011). nsp10-mediated activation of nsp16 catalytic activity is conserved in all coronaviruses (Wang et al. 2015). The same binding surface of nsp10 interacts with nsp14 and nsp16, suggesting that binding of nsp14 and nsp16 to nsp10 is mutually exclusive. However, as nsp10 is produced in a higher number of copies than nsp14 and nsp16, and as nsp14 and nsp16 act coordinately in RNA capping, it is most likely that nsp14:nsp10 and nsp16:nsp10 complexes co-exist within the viral replication-transcription complex (RTC) (Bouvet et al. 2012, Bouvet et al. 2014). One structural study reported that nsp10 forms dodecamers (Su et al. 2006), which would potentially allow simultaneous binding of nsp14 and nsp16 to nsp10 homomeric complexes, but it is not certain if such homomeric complexes of nsp10 exist in vivo, and if the structure of the nsp10 dodecamer would be permissive for nsp16 binding (Chen et al. 2011). nsp10 contains two zinc fingers which are thought to be involved in RNA binding (Su et al. 2006, Joseph et al. 2006).

Literature References
PubMed ID Title Journal Year
20421945 In vitro reconstitution of SARS-coronavirus mRNA cap methylation

Bouvet, M, Debarnot, C, Imbert, I, Selisko, B, Snijder, EJ, Canard, B, Decroly, E

PLoS Pathog. 2010
21637813 Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex

Decroly, E, Debarnot, C, Ferron, F, Bouvet, M, Coutard, B, Imbert, I, Gluais, L, Papageorgiou, N, Sharff, A, Bricogne, G, Ortiz-Lombardia, M, Lescar, J, Canard, B

PLoS Pathog. 2011
26041293 Coronavirus nsp10/nsp16 Methyltransferase Can Be Targeted by nsp10-Derived Peptide In Vitro and In Vivo To Reduce Replication and Pathogenesis

Wang, Y, Sun, Y, Wu, A, Xu, S, Pan, R, Zeng, C, Jin, X, Ge, X, Shi, Z, Ahola, T, Chen, Y, Guo, D

J. Virol. 2015
21393853 Crystallization and diffraction analysis of the SARS coronavirus nsp10-nsp16 complex

Debarnot, C, Imbert, I, Ferron, F, Gluais, L, Varlet, I, Papageorgiou, N, Bouvet, M, Lescar, J, Decroly, E, Canard, B

Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2011
20699222 Molecular mapping of the RNA Cap 2'-O-methyltransferase activation interface between severe acute respiratory syndrome coronavirus nsp10 and nsp16

Lugari, A, Betzi, S, Decroly, E, Bonnaud, E, Hermant, A, Guillemot, JC, Debarnot, C, Borg, JP, Bouvet, M, Canard, B, Morelli, X, Lécine, P

J. Biol. Chem. 2010
22635272 RNA 3'-end mismatch excision by the severe acute respiratory syndrome coronavirus nonstructural protein nsp10/nsp14 exoribonuclease complex

Bouvet, M, Imbert, I, Subissi, L, Gluais, L, Canard, B, Decroly, E

Proc. Natl. Acad. Sci. U.S.A. 2012
22022266 Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2'-O-methylation by nsp16/nsp10 protein complex

Chen, Y, Su, C, Ke, M, Jin, X, Xu, L, Zhang, Z, Wu, A, Sun, Y, Yang, Z, Tien, P, Ahola, T, Liang, Y, Liu, X, Guo, D

PLoS Pathog. 2011
25074927 Coronavirus Nsp10, a critical co-factor for activation of multiple replicative enzymes

Bouvet, M, Lugari, A, Posthuma, CC, Zevenhoven, JC, Bernard, S, Betzi, S, Imbert, I, Canard, B, Guillemot, JC, Lécine, P, Pfefferle, S, Drosten, C, Snijder, EJ, Decroly, E, Morelli, X

J. Biol. Chem. 2014
Participants
Participates
Disease
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
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