Costa Alessandro, Onesti Silvia
Sir William Dunn School of Pathology, University of Oxford, UK.
Crit Rev Biochem Mol Biol. 2009 Sep-Oct;44(5):326-42. doi: 10.1080/10409230903186012.
The eukaryotic MCM2-7 complex is recruited onto origins of replication during the G1 phase of the cell cycle and acts as the main helicase at the replication fork during the S phase. Over the last few years a number of structural reports on MCM proteins using both electron microscopy and protein crystallography have been published. The crystal structures of two (almost) full-length archaeal homologs provide the first atomic pictures of a MCM helicase. However one of the structures is at low resolution and the other is of an inactive MCM. Moreover, both proteins are monomeric in the crystal, whereas the activity of the complex is critically dependent on oligomerization. Lower resolution structures derived from electron microscopy studies are therefore crucial to complement the crystallographic analysis and to assemble the multimeric complex that is active in the cell. A critical analysis of all the structural results elucidates the potential conformational changes and dynamic behavior of MCM helicase to provide a first insight into the gamut of molecular configurations adopted during the processes of DNA melting and unwinding.
真核生物的MCM2-7复合物在细胞周期的G1期被招募到复制起点，并在S期作为复制叉处的主要解旋酶发挥作用。在过去几年中，已经发表了许多使用电子显微镜和蛋白质晶体学对MCM蛋白进行的结构报告。两个（几乎）全长古菌同源物的晶体结构提供了MCM解旋酶的首张原子图像。然而，其中一个结构分辨率较低，另一个是无活性的MCM。此外，这两种蛋白质在晶体中都是单体，而复合物的活性关键取决于寡聚化。因此，来自电子显微镜研究的较低分辨率结构对于补充晶体学分析以及组装在细胞中具有活性的多聚体复合物至关重要。对所有结构结果的批判性分析阐明了MCM解旋酶潜在的构象变化和动态行为，从而首次深入了解DNA解链和展开过程中所采用的一系列分子构型。
