ABSTRACTHere, we report the three-dimensional structure of severe acute respiratory syndrome coronavirus (SARS-CoV) nsP7, a component of the SARS-CoV replicase polyprotein. The coronavirus replicase carries out regulatory tasks involved in the maintenance, transcription, and replication of the coronavirus genome. nsP7 was found to assume a compact architecture in solution, which is comprised primarily of helical secondary structures. Three helices (α2 to α4) form a flat up-down-up antiparallel α-helix sheet. The N-terminal segment of residues 1 to 22, containing two turns of α-helix and one turn of 310-helix, is packed across the surface of α2 and α3 in the helix sheet, with the α-helical region oriented at a 60° angle relative to α2 and α3. The surface charge distribution is pronouncedly asymmetrical, with the flat surface of the helical sheet showing a large negatively charged region adjacent to a large hydrophobic patch and the opposite side containing a positively charged groove that extends along the helix α1. Each of these three areas is thus implicated as a potential site for protein-protein interactions.