Alpha-N 甲基化是一种不寻常的“转录后”修饰，在其中，蛋白的氨基酸末端残基被甲基化。人们对其功能知之甚少，尽管在一个例子（即“Ran鸟嘌呤核甙酸-交换因子RCC1”）中甲基化是其与染色质结合所必需的。30多年前曾有人提出，也许存在一种真核α-N-specific甲基转移酶，而现在这样一种酶已在HeLa细胞中被发现。Schaner等人描述了第一种已知的α-N-甲基转移酶，名叫“N-terminal RCC1甲基转移酶” (NRMT)。他们识别出了“NRMT识别顺序”和几个新的甲基化目标，包括肿瘤抑制蛋白SET和视网膜母细胞瘤蛋白(Rb)。Alpha-N -甲基化还被发现是正常双极纺锤体形成及染色体分离所必需的。
生物谷推荐原文出处：
Nature doi:10.1038/nature09343
NRMT is an α-N-methyltransferase that methylates RCC1 and retinoblastoma protein
Christine E. Schaner Tooley,Janusz J. Petkowski,Tara L. Muratore-Schroeder,Jeremy L. Balsbaugh,Jeffrey Shabanowitz,Michal Sabat,Wladek Minor,Donald F. Hunt& Ian G. Macara
The post-translational methylation of α-amino groups was first discovered over 30 years ago on the bacterial ribosomal proteins L16 and L33 (refs 1, 2), but almost nothing is known about the function or enzymology of this modification. Several other bacterial and eukaryotic proteins have since been shown to be α-N-methylated3, 4, 5, 6, 7, 8, 9, 10. However, the Ran guanine nucleotide-exchange factor, RCC1, is the only protein for which any biological function of α-N-methylation has been identified3, 11. Methylation-defective mutants of RCC1 have reduced affinity for DNA and cause mitotic defects3, 11, but further characterization of this modification has been hindered by ignorance of the responsible methyltransferase. All fungal and animal N-terminally methylated proteins contain a unique N-terminal motif, Met-(Ala/Pro/Ser)-Pro-Lys, indicating that they may be targets of the same, unknown enzyme3, 12. The initiating Met is cleaved, and the exposed α-amino group is mono-, di- or trimethylated. Here we report the discovery of the first α-N-methyltransferase, which we named N-terminal RCC1 methyltransferase (NRMT). Substrate docking and mutational analysis of RCC1 defined the NRMT recognition sequence and enabled the identification of numerous new methylation targets, including SET (also known as TAF-I or PHAPII) and the retinoblastoma protein, RB. Knockdown of NRMT recapitulates the multi-spindle phenotype seen with methylation-defective RCC1 mutants3, demonstrating the importance of α-N-methylation for normal bipolar spindle formation and chromosome segregation.
