Myristyl amino-terminal acylation of murine retrovirus proteins: An unusual post-translational protein modification

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Abstract
The primary structure of the NH 2 -terminal region of the gag gene encoded internal membrane-associated protein p15 has been determined for both Rauscher and Moloney murine leukemia viruses. Peptides generated by endopeptidases and purified by HPLC were subjected to semi-automated Edman degradation. Dipeptides obtained with dipeptidyl carboxypeptidase were identified by gas chromatography-mass spectrometry. The amino acid sequence of the first 16-residue segment of Rauscher p15 is identical to the sequence of Moloney p15 except for a single amino acid substitution (Gly→Asp) at position 13. Both proteins were found to have an acylated NH 2 terminus. By mass spectroscopy, myristic acid [CH 3 (CH 2 ) 12 COOH] was found to be bound through an amide linkage to the NH 2 -terminal glycyl residue in both p15s. The results of liquid chromatography show that the NH 2 -terminal myristyl group greatly contributes to the strong binding of these modified proteins and peptides to hydrophobic surfaces. Because p15 is known to be derived from the NH 2 -terminal region of a precursor polyprotein Pr65 gag by proteolytic cleavage in the assembled virus, it is suggested that myristylation in vivo takes place during the biosynthesis of Pr65 gag . Preliminary data indicate that such modification of gag precursor polyproteins may be common to mammalian retroviruses. The role of NH 2 -terminal myristyl acylation of Pr65 gag in virus assembly and the possibility of similar NH 2 -terminal modifications of gag -related fusion proteins of transforming viruses are discussed.