Article
Progress in the structural and functional characterization of the coronavirus replicase complex: Crystal structure of the SARS-CoV Nsp9
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Published: | May 26, 2004 |
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In 2003, the SARS crisis has dramatically shown the scarcity of biochemical and structural data available regarding Coronaviruses. It is however anticipated that these data will greatly help anti-coronavirus drug-design, as examplified by recent work on the main protease. We are using a structural genomics approach aimed at determining the crystal structures of all the proteins encoded by the SARS-CoV genome. Currently, 28 ORFs or sub-ORFs have been targeted, and 20 proteins are in crystallization. Among those, 8 different SARS-CoV proteins, and 1 H229E-CoV have been crystallized. Here we report the crystal structure at 2.8 Å resolution of Nsp9 (113 residues), a protein from the replicase complex. Based on the crystal structure, its function has now been elucidated and awaits connection to a biological role in RNA metabolism. The crystal structure revealed that Nsp9 is a dimeric protein mainly consisting of b-strands and displaying a previously unreported overall folding resembling an OB-fold. Its partial similarity with trypsin-like proteases suggests that Nsp9 may have evolved from a protease ancestor. However, biochemical experiments support a role of Nsp9 in RNA binding, as predicted by an RNA track on the surface of the protein and relatedness with single-stranded nucleic acid binding (SSB) proteins. As this type of protein is unique in the RNA virus world, it may have a role in several processes such as recombination and the regulation of SARS-CoV replication/transcription.