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. 2020 Jul 29;5:131. doi: 10.1038/s41392-020-00241-4

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Structure of SARS-CoV-2 nsp10/nsp16 hetero-dimer. a Overall structure of the hetero-complex formed between nsp10 (magenta) and nsp16 (green). The secondary structural elements and the bound SAM molecule are labeled. b Superimposition of the nsp10/nsp16 structure of SARS-CoV-2 onto those of SARS-CoV (left panel, PDB: 3R24) and MERS-CoV (right panel, PDB: 5YN5). The color scheme for our structure is the same as in a, and the SARS-CoV and MERS-CoV structures are shown in gray. Those elements exhibiting variant conformations are highlighted and marked. c Detailed interactions at the nsp10/nsp16 binding interface. Dashed lines indicate hydrogen-bonds. d A magnified view on the two zinc-finger motifs in nsp10. e Detailed interactions between SAM and nsp16 at the SAM-binding pocket. f, g Interaction of SAM and SIN with SARS-CoV-2 nsp10/nsp16 characterized by differential scanning fluorimetry (DSF). The DSF data obtained with the protein-complex purified directly from E. coli (designated as co-expression) and the protein-complex after the denaturing-refolding cycle (designated as refolded) are shown in f and g, respectively. h–k Binding of SAM and SIN to SARS-CoV-2 nsp10/nsp16 characterized by isothermal titration calorimetry (ITC). h SAM to nsp10/nsp16 (co-expression). i SIN to nsp10/nsp16 (co-expression). j SAM to nsp10/nsp16 (refolded). k SIN to nsp10/nsp16 (refolded)