Structure of the N-terminal RNA-binding domain of the SARS CoV nucleocapsid protein.

Huang, Qiulong; Yu, Liping; Petros, Andrew M; Gunasekera, Angelo; Liu, Zhihong; Xu, Nan; Hajduk, Philip; Mack, Jamey; Fesik, Stephen W; Olejniczak, Edward T

The severe acute respiratory syndrome (SARS) virus belongs to the Coronaviridea family of viruses. Its virion encodes several proteins including a replicase and four structural proteins. Here we describe the three-dimensional structure of the N-terminal domain of the SARS coronavirus (CoV) nucleocapsid protein. The protein consists of a five-stranded beta sheet with a folding topology distinct from other RNA-binding proteins. Single-stranded RNAs bind to the protein surface at the junction between a flexible, positively charged beta hairpin and the core structure. NMR-based screening was used to identify low molecular weight compounds that bind to this site.