FIG. 1.

pp1a transmembrane domain prediction based on multiple alignment. The presence of transmembrane domains in the pp1a precursor was predicted (51) on the basis of a multiple alignment of 27 different coronavirus sequences with representatives from each of the different groups (RefSeq in the NCBI CoreNucleotide database). The resulting hydrophobicity plot is shown in the upper panel, with peaks reaching the threshold (dotted line) representing predicted membrane-spanning domains. The black line in the middle panel represents the protein and shows, based on the known topology of nsp4 (37), its predicted localization on the lumenal or cytoplasmic side of the membrane, which is symbolized by the gray bar. At the bottom, a schematic representation of pp1a is shown in which the regions containing the putative transmembrane (TM) domains, the papain-like protease (PLpro, two in MHV and one in SARS-CoV), and the main protease (Mpro) are highlighted. The protease cleavage sites are indicated by arrowheads, with the nsp3-encoded PLpro cleavage sites in gray and the nsp5-encoded Mpro cleavage sites in black.