Novel -barrel Fold in the NMR Structure of the Replicase Nonstructural Protein 1 from the SARS Coronavirus

Department of Molecular Biology, Consortium for Functional and Structural Proteomics of the SARS-CoV, and Joint Center for Structural Genomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA; Institut für Molekularbiologie und Biophysik, ETH Zürich, CH-8093 Zürich, Switzerland

^* To whom correspondence should be addressed. Email: wuthrich{at}scripps.edu.

	Abstract

The nonstructural protein 1 (nsp1) of the SARS coronavirus (CoV) has 179 residues and is the N-terminal cleavage product of the viral replicase polyprotein that mediates RNA replication and processing. The specific function of nsp1 is not known. Here we report the NMR structure of nsp1(13-128), which represents a novel /-fold formed by a mixed parallel/antiparallel 6-stranded -barrel, an -helix covering one opening of the barrel, and a 3₁₀-helix alongside the barrel. We further characterized the full-length 179-residue protein and show that the polypeptide segments of residues 1-12 and 129-179 are flexibly disordered. The structure is analyzed in a search for possible correlations with the recently reported activity of nsp1 in the degradation of mRNA.