The Saccharomyces cerevisiae Mcm6/2 and Mcm5/3 ATPase active sites contribute to the function of the putative Mcm2-7 'gate'.
The Saccharomyces cerevisiae Mcm6/2 and Mcm5/3 ATPase active sites contribute to the function of the putative Mcm2-7 'gate'.
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DOI：
10.1093/nar/gkq422
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发表时间：
2010-10
影响因子：
14.9
通讯作者：
Schwacha A
中科院分区：
文献类型：
--
作者：
Bochman ML;Schwacha A
Mcm 2 -7复合物是真核生物复制解旋酶，一种环形AAA+分子马达，在复制过程中使用三磷酸腺苷（ATP）结合和水解来分离双链DNA链。这种异源六聚体解旋酶包含六个不同的和必需的亚基（Mcm 2至Mcm 7），与相应的二聚体接口形成ATP酶活性位点从相邻亚基的保守基序。由于所有其他已知的六聚体解旋酶由六个相同的亚基形成，Mcm 2 -7独特的异源六聚体组织的功能是特别感兴趣的。事实上，先前的工作使用保守的步行者A盒ATP酶结构基序中的突变强烈表明，个别ATP酶活性位点对Mcm 2 -7活性的贡献不同。尽管解旋酶活性仅需要特定的活性位点子集，但另一个ATP酶活性位点（Mcm 2/5）可作为六聚体环结构内的可逆ATP依赖性不连续性（“门”）。本研究分析了另外两个结构基序，步行者B盒和精氨酸指，使每个Mcm 2 -7 ATP酶活性位点的贡献。这些图案的突变分析不仅证实，Mcm ATP酶活性位点的贡献不平等的活动，但牵连参与至少两个额外的活性位点（Mcm 5/3和6/2）在调制的推定Mcm 2/5门的活动。
The Mcm2-7 complex is the eukaryotic replicative helicase, a toroidal AAA+ molecular motor that uses adenosine triphosphate (ATP) binding and hydrolysis to separate duplex DNA strands during replication. This heterohexameric helicase contains six different and essential subunits (Mcm2 through Mcm7), with the corresponding dimer interfaces forming ATPase active sites from conserved motifs of adjacent subunits. As all other known hexameric helicases are formed from six identical subunits, the function of the unique heterohexameric organization of Mcm2-7 is of particular interest. Indeed, prior work using mutations in the conserved Walker A box ATPase structural motif strongly suggests that individual ATPase active sites contribute differentially to Mcm2-7 activity. Although only a specific subset of active sites is required for helicase activity, another ATPase active site (Mcm2/5) may serve as a reversible ATP-dependent discontinuity (‘gate’) within the hexameric ring structure. This study analyzes the contribution that two other structural motifs, the Walker B box and arginine finger, make to each Mcm2-7 ATPase active site. Mutational analysis of these motifs not only confirms that Mcm ATPase active sites contribute unequally to activity but implicates the involvement of at least two additional active sites (Mcm5/3 and 6/2) in modulating the activity of the putative Mcm2/5 gate.
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