Alpha-N 甲基化是一種不尋常的“轉(zhuǎn)錄后”修飾,，在其中，蛋白的氨基酸末端殘基被甲基化。人們對其功能知之甚少，盡管在一個例子（即“Ran鳥嘌呤核甙酸-交換因子RCC1”）中甲基化是其與染色質(zhì)結(jié)合所必需的,。30多年前曾有人提出,，也許存在一種真核α-N-specific甲基轉(zhuǎn)移酶,，而現(xiàn)在這樣一種酶已在HeLa細胞中被發(fā)現(xiàn)。Schaner等人描述了第一種已知的α-N-甲基轉(zhuǎn)移酶,，名叫“N-terminal RCC1甲基轉(zhuǎn)移酶” (NRMT),。他們識別出了“NRMT識別順序”和幾個新的甲基化目標，包括腫瘤抑制蛋白SET和視網(wǎng)膜母細胞瘤蛋白(Rb),。Alpha-N -甲基化還被發(fā)現(xiàn)是正常雙極紡錘體形成及染色體分離所必需的,。
生物谷推薦原文出處：
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.
