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分隔复杂结构可以由 ParB 二聚体的滑动和桥接产生。

Partition complex structure can arise from sliding and bridging of ParB dimers.

机构信息

Max Planck Institute for Terrestrial Microbiology and Center for Synthetic Microbiology, 35043, Marburg, Germany.

Department of Biology, University of Marburg, 35043, Marburg, Germany.

出版信息

Nat Commun. 2023 Jul 29;14(1):4567. doi: 10.1038/s41467-023-40320-y.

DOI:10.1038/s41467-023-40320-y
PMID:37516778
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10387095/
Abstract

In many bacteria, chromosome segregation requires the association of ParB to the parS-containing centromeric region to form the partition complex. However, the structure and formation of this complex have been unclear. Recently, studies have revealed that CTP binding enables ParB dimers to slide along DNA and condense the centromeric region through the formation of DNA bridges. Using semi-flexible polymer simulations, we demonstrate that these properties can explain partition complex formation. Transient ParB bridges organize DNA into globular states or hairpins and helical structures, depending on bridge lifetime, while separate simulations show that ParB sliding reproduces the multi-peaked binding profile observed in Caulobacter crescentus. Combining sliding and bridging into a unified model, we find that short-lived ParB bridges do not impede sliding and can reproduce both the binding profile and condensation of the nucleoprotein complex. Overall, our model elucidates the mechanism of partition complex formation and predicts its fine structure.

摘要

在许多细菌中,染色体分离需要 ParB 与包含 parS 的着丝粒区域结合,形成分区复合物。然而,这个复合物的结构和形成方式还不清楚。最近的研究表明,CTP 结合使 ParB 二聚体能够沿着 DNA 滑动,并通过形成 DNA 桥来浓缩着丝粒区域。我们使用半柔性聚合物模拟,证明了这些特性可以解释分区复合物的形成。瞬态 ParB 桥根据桥的寿命将 DNA 组织成球状状态或发夹和螺旋结构,而单独的模拟表明,ParB 滑动再现了在新月柄杆菌中观察到的多峰结合谱。将滑动和桥接结合到一个统一的模型中,我们发现短寿命的 ParB 桥不会阻碍滑动,并且可以再现核蛋白复合物的结合谱和浓缩。总的来说,我们的模型阐明了分区复合物形成的机制,并预测了其精细结构。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/10387095/007c24061fc0/41467_2023_40320_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/10387095/eedcdc9279da/41467_2023_40320_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/10387095/7ab1c11fb4fc/41467_2023_40320_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/10387095/50226b24ed3d/41467_2023_40320_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/10387095/f3de526b4912/41467_2023_40320_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/10387095/007c24061fc0/41467_2023_40320_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/10387095/eedcdc9279da/41467_2023_40320_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/10387095/7ab1c11fb4fc/41467_2023_40320_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/10387095/50226b24ed3d/41467_2023_40320_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/10387095/f3de526b4912/41467_2023_40320_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c95/10387095/007c24061fc0/41467_2023_40320_Fig5_HTML.jpg

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本文引用的文献

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2
ParB proteins can bypass DNA-bound roadblocks via dimer-dimer recruitment.ParB 蛋白可以通过二聚体-二聚体募集绕过 DNA 结合障碍。
Sci Adv. 2022 Jul;8(26):eabn3299. doi: 10.1126/sciadv.abn3299. Epub 2022 Jun 29.
3
Relief of ParB autoinhibition by DNA catalysis and recycling of ParB by CTP hydrolysis promote bacterial centromere assembly.通过DNA催化解除ParB自身抑制以及通过CTP水解实现ParB循环利用,促进细菌着丝粒组装。
Nucleic Acids Res. 2024 Jul 8;52(12):7321-7336. doi: 10.1093/nar/gkae450.
4
Mechanism of phase condensation for chromosome architecture and function.相分离机制在染色体结构与功能中的作用。
Exp Mol Med. 2024 Apr;56(4):809-819. doi: 10.1038/s12276-024-01226-x. Epub 2024 Apr 25.
5
Physical models of bacterial chromosomes.细菌染色体的物理模型。
Mol Microbiol. 2025 Feb;123(2):143-153. doi: 10.1111/mmi.15257. Epub 2024 Apr 5.
6
The virulence regulator VirB from Shigella flexneri uses a CTP-dependent switch mechanism to activate gene expression.福纳氏志贺菌的毒力调节因子 VirB 利用 CTP 依赖性开关机制激活基因表达。
Nat Commun. 2024 Jan 5;15(1):318. doi: 10.1038/s41467-023-44509-z.
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Connecting the dots: key insights on ParB for chromosome segregation from single-molecule studies.串联各个点:从单分子研究中得出的关于 ParB 用于染色体分离的关键见解。
FEMS Microbiol Rev. 2024 Jan 12;48(1). doi: 10.1093/femsre/fuad067.
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Nucleic Acids Res. 2023 Nov 27;51(21):11856-11875. doi: 10.1093/nar/gkad868.
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