nsp16 binds nsp10

Stable Identifier
R-HSA-9694445
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
cytosol
ReviewStatus
5/5
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nsp16 binds nsp10
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The interaction between the non-structural proteins nsp16 and nsp10 is conserved in SARS-CoV-2 virus (Li et al. 2020, Viswanathan et al. 2020, Rosas-Lemus et al. 2020; Xu et al, 2021).

In SARS-CoV-1, nsp16 was identified as 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). For efficient 2'-O-methyltransferase activity, two metal ions are bound by the complex. Both Mg2+ and Mn2+ show similarly optimal cofactor activities in vitro (Minasov et al, 2021).
Literature References
PubMed ID Title Journal Year
32511376 The crystal structure of nsp10-nsp16 heterodimer from SARS-CoV-2 in complex with S-adenosylmethionine

Jaroszewski, L, Maltseva, NI, Minasov, G, Wiersum, G, Joachimiak, A, Rosas-Lemus, M, Shuvalova, L, Godzik, A, Jedrzejczak, R, Kim, Y, Endres, M, Inniss, NL, Satchell, KJF, Kiryukhina, O

bioRxiv 2020
32838362 Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis

Liang, Q, Liu, C, Zhu, Z, Qu, Y, Zhu, T, Zhang, Y, Xiao, Z, Wu, P, Li, J, Yang, X, Yin, Y, Wang, C, Guo, M, Liu, Z, Tian, X, Wang, X, Peng, C

Med (N Y) 2020
34297909 Compartmentalization-aided interaction screening reveals extensive high-order complexes within the SARS-CoV-2 proteome

Xu, W, Li, P, Liu, H, Pei, G, Ju, X, Wang, J, Ding, Q

Cell Rep 2021
34131072 Mn2+ coordinates Cap-0-RNA to align substrates for efficient 2'-O-methyl transfer by SARS-CoV-2 nsp16

Brunzelle, JS, Minasov, G, Rosas-Lemus, M, Daczkowski, CM, Shuvalova, L, Hoover, P, Inniss, NL, Satchell, KJF, Mesecar, AD

Sci Signal 2021
32709886 Structural basis of RNA cap modification by SARS-CoV-2

Dai, N, Martínez-Sobrido, L, Kovalskyy, D, Chan, SH, Oladunni, F, Qi, S, Park, JG, Misra, A, Gupta, YK, Viswanathan, T, Hromas, RA, Arya, S

Nat Commun 2020
Participants
Input
Output
Participates
as an event of
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Authored
Orlic-Milacic, M  (2020-08-12)
Senff-Ribeiro, A  (2020-08-12)
Reviewed
Acencio, ML  (2020-09-09)
Created
Cook, J  (2020-07-07)
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