Identification of protein N-terminal methyltransferases in yeast and humans.
Identification of protein N-terminal methyltransferases in yeast and humans.
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DOI：
10.1021/bi100428x
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发表时间：
2010-06-29
期刊：
影响因子：
2.9
通讯作者：
Clarke, Steven G.
中科院分区：
文献类型：
--
作者：
Webb, Kristofor J.;Lipson, Rebecca S.;Al-Hadid, Qais;Whitelegge, Julian P.;Clarke, Steven G.
通过甲基化修饰蛋白质在细胞功能中是重要的。我们在这里表明，酿酒酵母YBR 261 C/TAE 1基因编码的N-末端蛋白甲基转移酶催化两个核糖体蛋白底物，Rpl12ab和Rps25a/Rps25b的修改。YBR261C/Tae1蛋白在真核生物中是保守的;所有这些蛋白与已知的七种β链I类甲基转移酶共享序列相似性。野生型酵母胞质溶胶和小鼠心脏胞质溶胶催化合成肽（PPKQQLSKY）的甲基化，所述合成肽含有经加工的Rps25 a/Rps25 b的N末端的前8个氨基酸。然而，在来自Δ YBR 261C/tae1缺失菌株的酵母胞质溶胶中未观察到该肽的甲基化。酵母YBR 261 C/TAE 1和人直系同源物胃L11 A基因在大肠杆菌中表达为融合蛋白，并显示能够化学计量地二甲基化合成肽的N-末端。此外，YBR 261 C/Tae 1和胃L11 A重组蛋白甲基化含有N-末端丙氨酸和丝氨酸残基的合成肽的变体。然而，当2位的脯氨酸残基或3位的赖氨酸残基被取代时，甲基转移酶活性在很大程度上被消除。因此，这里描述的甲基转移酶特异性地识别N-末端X-Pro-Lys序列基序，我们建议指定酵母酶Ntm1和人酶NTMT1。这些酶可以解释几乎所有先前描述的真核蛋白N-末端甲基化反应。许多其他酵母和人类蛋白质也共享识别基序，并且可以进行类似的修饰。我们的结论是，蛋白质X-Pro-Lys N-末端甲基化反应催化的酶在这里描述的可能是广泛的性质。
Protein modification by methylation is important in cellular function. We show here that the Saccharomyces cerevisiae YBR261C/TAE1 gene encodes an N-terminal protein methyltransferase catalyzing the modification of two ribosomal protein substrates, Rpl12ab and Rps25a/Rps25b. The YBR261C/Tae1 protein is conserved across eukaryotes; all of these proteins share sequence similarity with known seven beta strand class I methyltransferases. Wild type yeast cytosol and mouse heart cytosol catalyze the methylation of a synthetic peptide (PPKQQLSKY) that contains the first eight amino acids of the processed N-terminus of Rps25a/Rps25b. However, no methylation of this peptide is seen in yeast cytosol from a ΔYBR261C/tae1 deletion strain. Yeast YBR261C/TAE1 and the human ortholog METTL11A genes were expressed as fusion proteins in Escherichia coli and were shown to be capable of stoichiometrically dimethylating the N-terminus of the synthetic peptide. Furthermore, the YBR261C/Tae1 and METTL11A recombinant proteins methylate variants of the synthetic peptide containing N-terminal alanine and serine residues. However, methyltransferase activity is largely abolished when the proline residue in position 2 or the lysine residue in position 3 is substituted. Thus, the methyltransferases described here specifically recognize the N-terminal X-Pro-Lys sequence motif and we suggest designating the yeast enzyme Ntm1 and the human enzyme NTMT1. These enzymes may account for nearly all previously described eukaryotic protein N-terminal methylation reactions. A number of other yeast and humans proteins also share the recognition motif and may be similarly modified. We conclude that protein X-Pro-Lys N-terminal methylation reactions catalyzed by the enzymes described here may be widespread in nature.
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影响因子：
3.5
作者：
HENRY, GD;DALGARNO, DC;TRAYER, IP
通讯作者：
TRAYER, IP
影响因子：
4.4
作者：
Bergmueller, Eveline;Gehrig, Peter M.;Gruissem, Wilhelm
通讯作者：
Gruissem, Wilhelm
DOI：
10.1111/j.1432-1033.1975.tb02298.x
发表时间：
1975-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
HILL, GC;PETTIGREW, GW
通讯作者：
PETTIGREW, GW
DOI：
10.1111/j.1432-1033.1991.tb16012.x
发表时间：
1991-06-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
KMIECIK, D;BELAICHE, D;KERCKAERT, JP
通讯作者：
KERCKAERT, JP
影响因子：
4.8
作者：
Porras-Yakushi, TR;Whitelegge, JP;Clarke, S
通讯作者：
Clarke, S