Department of Structural Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 311, Memphis, TN, 38105, USA.
Incyte Research Institute, 1801 Augustine Cut-off, Wilmington, DE, 19803, USA.
Nat Commun. 2019 Jul 15;10(1):3117. doi: 10.1038/s41467-019-11074-3.
The DNA translocation activity of the minichromosome maintenance (MCM) complex powers DNA strand separation of the replication forks of eukaryotes and archaea. Here we illustrate an atomic level mechanism for this activity with a crystal structure of an archaeal MCM hexamer bound to single-stranded DNA and nucleotide cofactors. Sequence conservation indicates this rotary mechanism is fully possible for all eukaryotes and archaea. The structure definitively demonstrates the ring orients during translocation with the N-terminal domain leading, indicating that the translocation activity could also provide the physical basis of replication initiation where a double-hexamer idly encircling double-stranded DNA transforms to single-hexamers that encircle only one strand. In this mechanism, each strand binds to the N-terminal tier of one hexamer and the AAA+ tier of the other hexamer such that one ring pulls on the other, aligning equivalent interfaces to enable each hexamer to pull its translocation strand outside of the opposing hexamer.
DNA 迁移活动的微小染色体维持 (MCM) 复合物为真核生物和古菌的复制叉提供 DNA 链分离的动力。在这里，我们用一个晶体结构来阐明这种活性的原子水平机制，该结构是一个与单链 DNA 和核苷酸辅因子结合的古菌 MCM 六聚体。序列保守性表明，这种旋转机制在所有真核生物和古菌中都是完全可能的。该结构明确证明了环在迁移过程中的取向，即 N 端结构域领先，这表明迁移活性也可能为复制起始提供物理基础，在这种情况下，双六聚体闲置地环绕双链 DNA 转化为仅环绕一条链的单六聚体。在这个机制中，每一条链都与一个六聚体的 N 端层和另一个六聚体的 AAA+层结合，使得一个环拉动另一个环，使等效的界面对齐，从而使每个六聚体能够将其迁移链拉出与之相对的六聚体之外。
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