Transformation of MutL by ATP binding and hydrolysis: A switch in DNA mismatch repair
Transformation of MutL by ATP binding and hydrolysis: A switch in DNA mismatch repair
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DOI：
10.1016/s0092-8674(00)80717-5
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发表时间：
1999-04-02
期刊：
影响因子：
64.5
通讯作者：
Yang, W
中科院分区：
文献类型：
--
作者：
Ban, C;Junop, M;Yang, W
MutL DNA错配修复蛋白最近被证明是一种ATP酶，属于一个新兴的ATP酶超家族，包括DNA拓扑异构酶II和HSP 90。本文报道了E. coliMutL（LN 40）与底物类似物ADPs和产物ADP复合。脱辅基蛋白结构中无序的60多个残基变得有序，并有助于ADP结合和LN 40的二聚化。ATP的水解，通过随后释放γ-磷酸盐来表示，释放两个关键环并导致LN 40二聚体的解离。LN 40区域的二聚化是Mutt水解ATP所必需的，并且是Mutt水解ATP的限速步骤。MutL的ATP酶活性受到DNA的刺激，并且可能充当协调DNA错配修复的开关。
The MutL DNA mismatch repair protein has recently been shown to be an ATPase and to belong to an emerging ATPase superfamily that includes DNA topoisomerase II and Hsp90. We report here the crystal structures of a 40 kDa ATPase fragment of E. coli MutL (LN40) complexed with a substrate analog, ADPnP, and with product ADP. More than 60 residues that are disordered in the apoprotein structure become ordered and contribute to both ADPnP binding and dimerization of LN40. Hydrolysis of ATP, signified by subsequent release of the gamma-phosphate, releases two key loops and leads to dissociation of the LN40 dimer. Dimerization of the LN40 region is required for and is the rate-limiting step in ATP hydrolysis by Mutt. The ATPase activity of MutL is stimulated by DNA and likely acts as a switch to coordinate DNA mismatch repair.