Structure of a dimer of the Sulfolobus solfataricus MCM N-terminal domain reveals a potential role in MCM ring opening.
Structure of a dimer of the Sulfolobus solfataricus MCM N-terminal domain reveals a potential role in MCM ring opening.
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硫磺硫化叶菌 MCM N 末端结构域二聚体的结构揭示了 MCM 开环中的潜在作用。
DOI：
10.1107/s2053230x21005331
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Enemark,EricJ
中科院分区：
文献类型：
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作者：
Meagher,Martin;Spence,MadisonN;Enemark,EricJ
细胞强烈调节DNA复制，以确保基因组稳定性并预防包括癌症在内的多种疾病。真核生物和古生菌严格控制DNA复制起始，通过调节六聚体微型染色体维持（MCM）环的加载，以包围DNA双螺旋的两条链，然后调节加载环的活化，使得它们包围一条DNA链，同时排除另一条。这两个步骤都涉及开环/闭环转化，允许DNA链进入或退出。在这里，硫磺硫化叶菌MCM的N-末端结构域的二聚体的晶体结构与亚基间的接口，这是更广泛的比在闭环结构，同时包括共同的相互作用，使容易相互转换，提出。结果表明，所确定的接口可以稳定开放MCM环，通过补偿失去的相互作用在一个开放的邻居接口和先前的开放环低温EM结构的MCM加载具有类似的扩展接口附近的开放接口。
Cells strongly regulate DNA replication to ensure genomic stability and prevent several diseases, including cancers. Eukaryotes and archaea strictly control DNA-replication initiation by the regulated loading of hexameric minichromosome maintenance (MCM) rings to encircle both strands of the DNA double helix followed by regulated activation of the loaded rings such that they then encircle one DNA strand while excluding the other. Both steps involve an open/closed ring transformation, allowing DNA strands to enter or exit. Here, the crystal structure of a dimer of the N-terminal domain of Sulfolobus solfataricus MCM with an intersubunit interface that is more extensive than in closed-ring structures, while including common interactions to enable facile interconversion, is presented. It is shown that the identified interface could stabilize open MCM rings by compensating for lost interactions at an open neighbor interface and that the prior open-ring cryo-EM structure of MCM loading has a similar extended interface adjacent to its open interface.