MYRISTYL AMINO-TERMINAL ACYLATION OF MURINE RETROVIRUS PROTEINS - AN UNUSUAL POST-TRANSLATIONAL PROTEIN MODIFICATION
MYRISTYL AMINO-TERMINAL ACYLATION OF MURINE RETROVIRUS PROTEINS - AN UNUSUAL POST-TRANSLATIONAL PROTEIN MODIFICATION
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DOI：
10.1073/pnas.80.2.339
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发表时间：
1983-01-01
期刊：
影响因子：
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通讯作者：
OROSZLAN, S
中科院分区：
文献类型：
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作者：
HENDERSON, LE;KRUTZSCH, HC;OROSZLAN, S
已经确定了Rauscher和Moloney小鼠白血病病毒编码的内膜相关蛋白p15的gaggene的nh2末端区域的初级结构。利用高效液相色谱法（HPLC）纯化由内肽酶产生的肽段，进行半自动化Edman降解。二肽基羧肽酶合成的二肽采用气相色谱-质谱法进行鉴定。Rauscher p15的前16个残基片段的氨基酸序列与Moloney p15的序列完全相同，除了在第13位有一个单一的氨基酸取代（Gly→Asp）。这两种蛋白都被发现有一个酰基化的nh2末端。通过质谱分析，发现肉豆蔻酸[CH3(CH2)12COOH]通过酰胺键结合到两个p15s的nh2末端甘酰基残基上。液相色谱分析结果表明，nh2末端肉豆粕基对这些修饰蛋白和肽与疏水表面的强结合起了很大的作用。由于已知p15是由组装病毒中的前体多蛋白Pr65gag的nh2末端区域通过蛋白水解裂解而产生的，这表明在体内发生了Pr65gag的生物合成过程。初步数据表明，这种前体多蛋白修饰可能在哺乳动物逆转录病毒中很常见。讨论了nh2末端肉豆荚酰基化在Pr65gagin病毒组装中的作用，以及转化病毒中gag相关融合蛋白类似nh2末端修饰的可能性。
The primary structure of the NH2-terminal region of thegaggene 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 NH2terminus. 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 Pr65gagby proteolytic cleavage in the assembled virus, it is suggested that myristylationin vivotakes place during the biosynthesis of Pr65gag. Preliminary data indicate that such modification ofgagprecursor polyproteins may be common to mammalian retroviruses. The role of NH2-terminal myristyl acylation of Pr65gagin virus assembly and the possibility of similar NH2-terminal modifications ofgag-related fusion proteins of transforming viruses are discussed.