Composite active site of an ABC ATPase: MutS uses ATP to verify mismatch recognition and authorize DNA repair
Composite active site of an ABC ATPase: MutS uses ATP to verify mismatch recognition and authorize DNA repair
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DOI：
10.1016/s1097-2765(01)00149-6
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发表时间：
2001-01-01
期刊：
影响因子：
16
通讯作者：
Yang, W
中科院分区：
文献类型：
--
作者：
Junop, MS;Obmolova, G;Yang, W
MutS蛋白通过识别嵌入双链体DNA中的错配和未配对碱基并激活内切核酸酶和外切核酸酶以去除错配来启动DNA错配修复。MutS家族的成员还具有属于ATP结合盒（ABC）超家族的保守ATP酶活性。在这里，我们报告了MutS-DNA-ADP三元复合物的晶体结构，以及通过诱变干扰复合ATP酶活性位点来启动错配修复的测定。这些研究表明，MutS必须同时结合ATP和错配DNA才能激活其他错配修复蛋白。我们认为MutS ATP酶活性在DNA错配修复、错配识别验证和修复授权中发挥着校对作用。
The MutS protein initiates DNA mismatch repair by recognizing mispaired and unpaired bases embedded in duplex DNA and activating endo- and exonucleases to remove the mismatch. Members of the MutS family also possess a conserved ATPase activity that belongs to the ATP binding cassette (ABC) superfamily. Here we report the crystal structure of a ternary complex of MutS-DNA-ADP and assays of initiation of mismatch repair in conjunction with perturbation of the composite ATPase active site by mutagenesis. These studies indicate that MutS has to bind both ATP and the mismatch DNA simultaneously in order to activate the other mismatch repair proteins. We propose that the MutS ATPase activity plays a proofreading role in DNA mismatch repair, verification of mismatch recognition, and authorization of repair.