Insights into the Architecture of the Replicative Helicase from the Structure of an Archaeal MCM Homolog
Insights into the Architecture of the Replicative Helicase from the Structure of an Archaeal MCM Homolog
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DOI：
10.1016/j.str.2008.11.010
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发表时间：
2009-02-13
期刊：
影响因子：
5.7
通讯作者：
Nair, Satish K.
中科院分区：
文献类型：
--
作者：
Bae, Brian;Chen, Yi-Hsing;Nair, Satish K.
微染色体维持（MCM）蛋白是AAA+（与多种细胞活性相关的ATP酶）超家族的成员，被认为是真核生物和古细菌中的复制解旋酶。在这里，我们提出了1.9 A的分辨率晶体结构的单体MCM同系物从Methanopyrus kandleri，第一个晶体结构的全长MCM。我们还提出了一个18埃冷冻电子显微镜重建的六聚体MCM从甲烷热细菌thermautotrophicus，并适合原子分辨率的晶体结构到重建，以产生一个原子模型的低聚体组装。这些结构数据揭示了一个独特的活性位点拓扑结构组成的一个独特的安排的关键决定因素。这些结构还提供了一个分子框架，用于理解反式作用元件的功能贡献，这些反式作用元件促进了响应于DNA结合和ATP水解的亚基间串扰。
The minichromosome maintenance (MCM) proteins, members of the AAA+ (ATPase associated with diverse cellular activities) superfamily, are believed to constitute the replicative helicase in eukaryotic and archaeal species. Here, we present the 1.9 A resolution crystal structure of a monomeric MCM homolog from Methanopyrus kandleri, the first crystallographic structure of a full-length MCM. We also present an 18 angstrom cryo-electron microscopy reconstruction of the hexameric MCM from Methanothermobacter thermautotrophicus, and fit the atomic resolution crystal structure into the reconstruction in order to generate an atomic model for the oligomeric assembly. These structural data reveal a distinct active site topology consisting of a unique arrangement of critical determinants. The structures also provide a molecular framework for understanding the functional contributions of trans-acting elements that facilitate intersubunit crosstalk in response to DNA binding and ATP hydrolysis.