Structural basis and functional analysis of the SARS coronavirus nsp14–nsp10 complex

• DOI: 10.1073/pnas.1508686112
• Publication Date: 2015-07-10T03:10:58Z
• Authors: Yuanyuan Ma; Lijie Wu; Neil Shaw; Yan Gao; Jin Wang; Yuna Sun; Zhiyong Lou; Liming Yan; Rongguang Zhang; Zihe Rao
• Keywords: Models, Molecular; 0303 health sciences; Multidisciplinary; Sequence Homology, Amino Acid; Molecular Sequence Data; Zinc Fingers; Methyltransferases; Viral Nonstructural Proteins; Ligands; Virus Replication; Protein Structure, Secondary; Protein Structure, Tertiary; 3. Good health; 03 medical and health sciences; Severe acute respiratory syndrome-related coronavirus; Exoribonucleases; Escherichia coli; RNA, Viral; Amino Acid Sequence; RNA, Messenger

Significance Proofreading exonucleases contributing to replication fidelity in DNA viruses and cellular organisms are well known; however, proofreading in RNA viruses was unknown until recently. Coronavirus nonstructural protein 14 (nsp14) has been shown to function as a proofreading exoribonuclease. Additionally, nsp14 shows (guanine-N7) methyl transferase activity for viral mRNA capping. Both roles are important for viral replication and transcription. Here, we report the structures of severe acute respiratory syndrome-coronavirus nsp14 in complex with its activator nonstructural protein 10 (nsp10) and functional ligands. Structural observations coupled with mutagenesis and functional assays provide a better understanding of the function of nsp14. Furthermore, the structures of the nsp14–nsp10 complex demonstrate several unique niches that could be targeted for development of potent antiviral drugs.