3R24

Crystal structure of nsp10/nsp16 complex of SARS coronavirus

Summary for 3R24

• Entry DOI: 10.2210/pdb3r24/pdb
• Descriptor: 2'-O-methyl transferase, Non-structural protein 10 and Non-structural protein 11, S-ADENOSYLMETHIONINE, ... (5 entities in total)
• Functional Keywords: methyltransferase, zinc-finger, transferase, viral protein
• Biological source: SARS coronavirus (SARS-CoV); More
• Total number of polymer chains: 2
• Total formula weight: 55928.39

Authors

Liu, X.,Guo, D.,Su, C.,Chen, Y. (deposition date: 2011-03-13, release date: 2011-10-26, Last modification date: 2024-02-21)

Primary citation

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.
Biochemical and structural insights into the mechanisms of SARS coronavirus RNA ribose 2'-O-methylation by nsp16/nsp10 protein complex.
Plos Pathog., 7:e1002294-e1002294, 2011

PubMed Abstract: The 5'-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5'-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2'-O positions, catalyzed by nsp14 N7-MTase and nsp16 2'-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2'-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs.

PubMed: 22022266
DOI: 10.1371/journal.ppat.1002294

Experimental method

X-RAY DIFFRACTION (2 Å)