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

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The primary structure of the NH2-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 NH2 terminus. By mass spectroscopy, myristic acid [CH3(CH2)12COOH] was found to be bound through an amide linkage to the NH2-terminal glycyl residue in both p15s. The results of liquid chromatography show that the NH2-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 NH2-terminal region of a precursor polyprotein Pr65gag by proteolytic cleavage in the assembled virus, it is suggested that myristylation in vivo takes place during the biosynthesis of Pr65gag. Preliminary data indicate that such modification of gag precursor polyproteins may be common to mammalian retroviruses. The role of NH2-terminal myristyl acylation of Pr65gag in virus assembly and the possibility of similar NH2-terminal modifications of gag-related fusion proteins of transforming viruses are discussed.

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