研究解析祖先型解旋酶装载因子 DciA 打开 DnaB 环的结构基础
Structural basis of DnaB ring opening by the ancestral helicase loader DciA
研究通过 3.5 Å 冷冻电镜结构解析了 DnaB6·DciA3 复合物，揭示 DciA 如何重塑细菌复制解旋酶 DnaB。多数细菌缺乏经典 AAA+ 解旋酶装载因子，而依赖进化上保守、不依赖 ATP 的 DciA，其机制此前不清楚。结构显示 DciA 结合在解旋酶外周，稳定一种右手开放螺旋构象，仅有一个界面裂开；三个 DciA 分子对接在交替的 linker-helix/docking-helix 模块上，其中一个 N 端结构域（NTD）作用于裂开的界面，占据被移位的 linker helix 让出的口袋，充当楔子促进环打开。
来源：Nucleic Acids Research · doi.org
Ring-shaped helicases must be opened and loaded onto DNA to initiate genome replication. In bacteria, most species lack canonical AAA+ helicase loaders and instead rely on DciA, an evolutionarily conserved, ATP-independent factor whose mechanism has remained unclear. Here we define how DciA remodels the bacterial replicative helicase DnaB. A 3.5 Å cryo-EM structure reveals a DnaB6·DciA3 complex in which DciA binds the periphery of the helicase and stabilizes a right-handed open-helical conformation with a single cracked interface. Three DciA molecules dock onto alternate linker-helix/docking-helix modules, while one N-terminal domain (NTD) engages the cracked interface, occupying the pocket vacated by the displaced linker helix and acting as a wedge to promote ring opening. Functional analyses reveal how DciA couples ATPase suppression with efficient helicase loading through coordinated actions of its NTDs and C-terminal domains. Together, these findings define a minimal, ATP-independent mechanism for helicase loading and show how an ancestral loader remodels DnaB to overcome a fundamental topological barrier.