Structure of protein phosphatase methyltransferase 1 (PPM1), a leucine carboxyl methyltransferase involved in the regulation of protein phosphatase 2A activity
Structure of protein phosphatase methyltransferase 1 (PPM1), a leucine carboxyl methyltransferase involved in the regulation of protein phosphatase 2A activity
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DOI：
10.1074/jbc.m311484200
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发表时间：
2004-02-27
影响因子：
4.8
通讯作者：
van Tilbeurgh, H
中科院分区：
文献类型：
--
作者：
Leulliot, N;Quevillon-Cheruel, S;van Tilbeurgh, H
丝氨酸/苏氨酸蛋白磷酸酶2A（PP 2A）在各种细胞过程中的重要作用需要PP 2A活性、定位和底物特异性的精确和动态调节。PP 2A功能的调节涉及催化亚基的C-末端亮氨酸的COOH基团的可逆甲基化，这反过来控制酶的异源多聚体组成并赋予不同的蛋白质识别和底物特异性。我们已经确定了PPM 1的结构，PPM 1是负责PP 2A甲基化的酵母甲基转移酶。PPM 1的结构揭示了一个共同的S-腺苷-L-甲硫氨酸依赖性甲基转移酶折叠，具有几个插入，赋予特定的功能和底物识别。与S-腺苷-L-甲硫氨酸甲基供体和S-腺苷-L-高半胱氨酸产物和抑制剂的复合物明确地揭示了共底物结合位点，并为PP 2A C-末端肽结合位点提供了令人信服的假设。第二种晶体形式的PPM 1的结构为PPM 1/PP 2A相互作用的动态性质提供了线索。
The important role of the serine/threonine protein phosphatase 2A (PP2A) in various cellular processes requires a precise and dynamic regulation of PP2A activity, localization, and substrate specificity. The regulation of the function of PP2A involves the reversible methylation of the COOH group of the C-terminal leucine of the catalytic subunit, which, in turn, controls the enzyme's heteromultimeric composition and confers different protein recognition and substrate specificity. We have determined the structure of PPM1, the yeast methyltransferase responsible for methylation of PP2A. The structure of PPM1 reveals a common S-adenosyl-L-methionine- dependent methyltransferase fold, with several insertions conferring the specific function and substrate recognition. The complexes with the S-adenosyl-L-methionine methyl donor and the S-adenosyl-L-homocysteine product and inhibitor unambiguously revealed the co-substrate binding site and provided a convincing hypothesis for the PP2A C-terminal peptide binding site. The structure of PPM1 in a second crystal form provides clues to the dynamic nature of the PPM1/PP2A interaction.