Paik W K, Cho Y B, Frost B, Kim S
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140.
Biochem Cell Biol. 1989 Sep;67(9):602-11. doi: 10.1139/o89-093.
In this review, protein methylation is outlined in general terms, highlighting the major amino acids that are methylated and some of the proteins in which they are found. The majority of the review examines the methylation of cytochrome c at Lys-77 of lower eukaryotes as a possible model for methylation studies. Early work involving the purification and characterization of the methyltransferase responsible for this methylation indicated cytochrome c was methylated posttranslationally, yet prior to import into the mitochondria. Methylation in vitro occurred only at the in vivo methylation site and only on cytochrome c. Later studies using in vitro translated apocytochrome c revealed that methylated, as compared with unmethylated, apocytochrome c was imported preferentially into yeast, but not rat liver, mitochondria. Efforts to discover the reasons for this preference have shown that methylation of apocytochrome c dramatically lowers its isoelectric point (against a predicted increase) and decrease its Stokes radius. A possible mechanism for these differences involving the disruption of hydrogen bonds is presented here with space-filling models. Finally, the in vivo significance of this modification is also discussed.
在本综述中，蛋白质甲基化将从总体上进行概述，重点介绍发生甲基化的主要氨基酸以及发现这些氨基酸的部分蛋白质。本综述的大部分内容探讨了低等真核生物细胞色素c赖氨酸77位的甲基化，将其作为甲基化研究的一个可能模型。早期涉及负责这种甲基化的甲基转移酶的纯化和特性研究表明，细胞色素c在翻译后、导入线粒体之前发生甲基化。体外甲基化仅发生在体内甲基化位点，且仅发生在细胞色素c上。后来使用体外翻译的脱辅基细胞色素c的研究表明，与未甲基化的脱辅基细胞色素c相比，甲基化的脱辅基细胞色素c优先导入酵母线粒体，但不导入大鼠肝脏线粒体。为找出这种偏好的原因所做的努力表明，脱辅基细胞色素c的甲基化显著降低了其等电点（与预测的升高相反）并减小了其斯托克斯半径。本文用空间填充模型展示了一种涉及氢键破坏的这些差异的可能机制。最后，还讨论了这种修饰在体内的意义。
