Structure of alphacoronavirus TGEV nsp 1 has implications for 1 coronavirus nsp 1 function and evolution

9 Coronavirus nsp1 have been shown to induce suppression of host mRNA expression 10 and to interfere with host immune response. However, the mechanism is currently 11 unknown. The only available structural information on coronavirus nsp1 is the NMR 12 structure of the N-terminal domain of nsp1 from severe acute respiratory syndrom 13 coronavirus (SARS-CoV) from the genus betacoronavirus. Here we present the first 14 nsp1 structure from an alphacoronavirus, TGEV nsp1. It displays a six-stranded 15 β-barrel fold with a long alpha helix on the rim of the barrel, a fold shared with 16 SARS-CoV nsp1. Contrary to previous speculation, the TGEV nsp1 structure 17 suggests that coronavirus nsp1s have a common origin, despite the lack of sequence 18 homology. However, comparisons of surface electrostatics, shape and amino acid 19 conservation between the alphaand betacoronaviruses lead us to speculate that the 20 mechanism for nsp1 induced suppression of host mRNA expression might be 21 different in these two genera. 22 23