title: Structure of alphacoronavirus transmissible gastroenteritis virus nsp1 has implications for coronavirus nsp1 function and evolution.
abstract: Coronavirus nsp1 has been shown to induce suppression of host gene expression and to interfere with the host immune response. However, the mechanism is currently unknown. The only available structural information on coronavirus nsp1 is the nuclear magnetic resonance (NMR) structure of the N-terminal domain of nsp1 from severe acute respiratory syndrome coronavirus (SARS-CoV) from the betacoronavirus genus. Here we present the first nsp1 structure from an alphacoronavirus, transmissible gastroenteritis virus (TGEV) nsp1. It displays a six-stranded β-barrel fold with a long alpha helix on the rim of the barrel, a fold shared with SARS-CoV nsp1(13-128). Contrary to previous speculation, the TGEV nsp1 structure suggests that coronavirus nsp1s have a common origin, despite the lack of sequence homology. However, comparisons of surface electrostatics, shape, and amino acid conservation between the alpha- and betacoronaviruses lead us to speculate that the mechanism for nsp1-induced suppression of host gene expression might be different in these two genera.
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Uppsala, Sweden. anna.jansson@icm.uu.se
authors.forename: Anna M
authors.initials: AM
authors.lastname: Jansson
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D015870:Gene Expression; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D005760:Transmissible gastroenteritis virus / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D017361:Viral Nonstructural Proteins; C521592:Nsp1 protein, SARS coronavirus; D012324:RNA-Dependent RNA Polymerase