PEPTIDE SUBSTRATE CLEAVAGE SPECIFICITY OF THE HUMAN CYTOMEGALOVIRUS PROTEASE

The human cytomegalovirus UL80 gene encodes an 80-kDa precursor polypr otein whose N-terminal 256-amino acid domain is a protease. This enzym e cleaves a specific peptide bond that results in its own release from the precursor, as well as a peptide bond near the C terminus of the v iral assembly protein. The latter cleavage is apparently required for encapsidation of the viral genomic DNA and maturation of the viral cap sid. A series of peptide substrates, representing the assembly protein cleavage site, was used to study the enzyme's substrate requirements and specificity. It was found that efficient cleavage minimally requir ed the amino acid residues spanning the P4 to P4' positions. Substitut ion at any of these residues adversely affected the reaction. Conserva tion of the hydrophobic residues at P3 and P4 was essential. In additi on, cleavage of a peptide representing the protease domain release sit e was reduced almost 100-fold relative to cleavage of the assembly pro tein maturation site peptide substrate.