ENDOPROTEOLYSIS OF NON-CAAX-CONTAINING ISOPRENYLATED PEPTIDES

A microsomal endoprotease specifically cleaves isoprenylated peptides of the CAAX motif, such as N-acetyl-S-all-trans-farnesyl-L-cysteine (A FC-VIM), at the isoprenylated cysteine residue:lt is shown here that e ndoproteolysis will also occur with peptides which are not of the CAAX type. Peptide substrates modeled after the Delta virus large antigen carboxyl-terminus (CRPQ) are endoproteolytically hydrolyzed by liver m icrosomes. AFC-RPQ is hydrolyzed with a K(M) = 12.4 muM and a V(max) = 0.27 nmol/min/mg, and AGGC-RPQ is hydrolyzed with a K(M) = 7.9 muM an d a V(max) = 0.042 nmol/min/mg. Moreover, a series of potent inhibitor s of the endoproteolysis of AFC-AAX-containing peptides are ineffectiv e at inhibiting the hydrolysis of AFC-RPQ and AGGC-RPQ, suggesting the existence of isoforms of the endoprotease.