• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

人类核心着丝粒核小体复合物的结构。

Structure of the Human Core Centromeric Nucleosome Complex.

机构信息

Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Curr Biol. 2019 Aug 19;29(16):2625-2639.e5. doi: 10.1016/j.cub.2019.06.062. Epub 2019 Jul 25.

DOI:10.1016/j.cub.2019.06.062
PMID:31353180
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6702948/
Abstract

Centromeric nucleosomes are at the interface of the chromosome and the kinetochore that connects to spindle microtubules in mitosis. The core centromeric nucleosome complex (CCNC) harbors the histone H3 variant, CENP-A, and its binding proteins, CENP-C (through its central domain; CD) and CENP-N (through its N-terminal domain; NT). CENP-C can engage nucleosomes through two domains: the CD and the CENP-C motif (CM). CENP-C is part of the CCNC by virtue of its high specificity for CENP-A nucleosomes and ability to stabilize CENP-A at the centromere. CENP-C is thought to engage a neighboring nucleosome, either one containing conventional H3 or CENP-A, and a crystal structure of a nucleosome complex containing two copies of CENP-C was reported. Recent structures containing a single copy of CENP-N bound to the CENP-A nucleosome in the absence of CENP-C were reported. Here, we find that one copy of CENP-N is lost for every two copies of CENP-C on centromeric chromatin just prior to kinetochore formation. We present the structures of symmetric and asymmetric forms of the CCNC that vary in CENP-N stoichiometry. Our structures explain how the central domain of CENP-C achieves its high specificity for CENP-A nucleosomes and how CENP-C and CENP-N sandwich the histone H4 tail. The natural centromeric DNA path in our structures corresponds to symmetric surfaces for CCNC assembly, deviating from what is observed in prior structures using artificial sequences. At mitosis, we propose that CCNC asymmetry accommodates its asymmetric connections at the chromosome/kinetochore interface. VIDEO ABSTRACT.

摘要

着丝粒核小体位于染色体与纺锤体微管相连的动粒的交界处。核心着丝粒核小体复合物（CCNC）含有组蛋白 H3 变体 CENP-A 及其结合蛋白 CENP-C（通过其中心结构域；CD）和 CENP-N（通过其 N 端结构域；NT）。CENP-C 可以通过两个结构域与核小体结合：CD 和 CENP-C 基序（CM）。CENP-C 是 CCNC 的一部分，因为它对 CENP-A 核小体具有高度特异性，并能够稳定着丝粒处的 CENP-A。CENP-C 被认为与相邻核小体结合，该核小体可以是含有常规 H3 或 CENP-A 的核小体，并且报告了含有两个 CENP-C 拷贝的核小体复合物的晶体结构。最近的结构报告了在没有 CENP-C 的情况下，单个 CENP-N 拷贝与 CENP-A 核小体结合。在这里，我们发现，在动粒形成之前，在着丝粒染色质上，每两个 CENP-C 拷贝就会丢失一个 CENP-N 拷贝。我们展示了 CENP-N 化学计量变化的 CCNC 的对称和不对称形式的结构。我们的结构解释了 CENP-C 的中心结构域如何实现其对 CENP-A 核小体的高度特异性，以及 CENP-C 和 CENP-N 如何夹住组蛋白 H4 尾巴。我们的结构中的天然着丝粒 DNA 路径对应于 CCNC 组装的对称表面，与使用人工序列的先前结构中观察到的不同。在有丝分裂期间，我们提出 CCNC 的不对称性适应了其在染色体/动粒界面的不对称连接。视频摘要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/227051890a89/nihms-1534627-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/87b3c22c19fd/nihms-1534627-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/5327343bca6d/nihms-1534627-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/b16105f5dc13/nihms-1534627-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/edaa39075765/nihms-1534627-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/06d30d6a0a26/nihms-1534627-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/e82e90eb1da0/nihms-1534627-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/227051890a89/nihms-1534627-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/87b3c22c19fd/nihms-1534627-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/5327343bca6d/nihms-1534627-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/b16105f5dc13/nihms-1534627-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/edaa39075765/nihms-1534627-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/06d30d6a0a26/nihms-1534627-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/e82e90eb1da0/nihms-1534627-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae85/6702948/227051890a89/nihms-1534627-f0007.jpg

相似文献

1
Structure of the Human Core Centromeric Nucleosome Complex.人类核心着丝粒核小体复合物的结构。
Curr Biol. 2019 Aug 19;29(16):2625-2639.e5. doi: 10.1016/j.cub.2019.06.062. Epub 2019 Jul 25.
2
Tetrameric organization of vertebrate centromeric nucleosomes.脊椎动物着丝粒核小体的四聚体结构。
Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20317-22. doi: 10.1073/pnas.1009563107. Epub 2010 Nov 8.
3
The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle.着丝粒成为焦点：从 CENP-A 核小体到与纺锤体的动粒连接。
Open Biol. 2020 Jun;10(6):200051. doi: 10.1098/rsob.200051. Epub 2020 Jun 10.
4
Cryo-EM Structures of Centromeric Tri-nucleosomes Containing a Central CENP-A Nucleosome.含有中央着丝粒 CENP-A 核小体的着丝粒三核小体的低温电镜结构。
Structure. 2020 Jan 7;28(1):44-53.e4. doi: 10.1016/j.str.2019.10.016. Epub 2019 Nov 8.
5
Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N.动粒蛋白 CENP-N 识别着丝粒核小体的结构机制。
Science. 2018 Jan 19;359(6373):339-343. doi: 10.1126/science.aar2781. Epub 2017 Dec 21.
6
Cryo-EM structure of the CENP-A nucleosome in complex with phosphorylated CENP-C.冷冻电镜结构解析的 CENP-A 核小体与磷酸化的 CENP-C 的复合物。
EMBO J. 2021 Mar 1;40(5):e105671. doi: 10.15252/embj.2020105671. Epub 2021 Jan 19.
7
Crystal structure of the human centromeric nucleosome containing CENP-A.人类着丝粒核小体中含 CENP-A 的晶体结构。
Nature. 2011 Jul 10;476(7359):232-5. doi: 10.1038/nature10258.
8
Structure of the human inner kinetochore CCAN complex and its significance for human centromere organization.人类内着丝粒 CCAN 复合物的结构及其对人类着丝粒组织的意义。
Mol Cell. 2022 Jun 2;82(11):2113-2131.e8. doi: 10.1016/j.molcel.2022.04.027. Epub 2022 May 6.
9
Centromere DNA Destabilizes H3 Nucleosomes to Promote CENP-A Deposition during the Cell Cycle.着丝粒 DNA 破坏 H3 核小体以促进细胞周期中 CENP-A 的沉积。
Curr Biol. 2018 Dec 17;28(24):3924-3936.e4. doi: 10.1016/j.cub.2018.10.049. Epub 2018 Nov 29.
10
Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome.内着丝粒 CCAN 复合物在着丝粒核小体上的组装结构。
Nature. 2019 Oct;574(7777):278-282. doi: 10.1038/s41586-019-1609-1. Epub 2019 Oct 2.

引用本文的文献

1
Regulation of M18BP1 centromeric localization and CENP-A assembly.M18BP1着丝粒定位与CENP-A组装的调控
bioRxiv. 2025 Jul 15:2025.07.15.664882. doi: 10.1101/2025.07.15.664882.
2
Cohesin-mediated stabilization of the CCAN complex at kinetochores in mitosis.有丝分裂过程中黏连蛋白介导的着丝粒处CCAN复合体的稳定。
Curr Biol. 2025 Jul 22. doi: 10.1016/j.cub.2025.07.011.
3
Cold-induced nucleosome dynamics linked to silencing of Arabidopsis FLC.低温诱导的核小体动力学与拟南芥FLC基因沉默相关

本文引用的文献

1
Genetic screening identifies a SUMO protease dynamically maintaining centromeric chromatin.遗传筛选鉴定出一种 SUMO 蛋白酶，该蛋白酶可动态维持着着丝粒染色质。
Nat Commun. 2020 Jan 24;11(1):501. doi: 10.1038/s41467-019-14276-x.
2
Human Artificial Chromosomes that Bypass Centromeric DNA.人类人工染色体，绕过着丝粒 DNA。
Cell. 2019 Jul 25;178(3):624-639.e19. doi: 10.1016/j.cell.2019.06.006.
3
DNA replication acts as an error correction mechanism to maintain centromere identity by restricting CENP-A to centromeres.DNA 复制作为一种纠错机制，通过将 CENP-A 限制在着丝粒上来维持着丝粒的身份。
Nat Commun. 2025 Jul 1;16(1):5550. doi: 10.1038/s41467-025-60735-z.
4
Solution conformational differences between conventional and CENP-A nucleosomes are accentuated by reversible deformation under high pressure.在高压下的可逆变形会加剧传统核小体与着丝粒蛋白A核小体之间的溶液构象差异。
Chromosome Res. 2025 Jun 12;33(1):11. doi: 10.1007/s10577-025-09769-z.
5
Cryo-EM Analysis of a Unique Subnucleosome Containing Centromere-Specific Histone Variant CENP-A.含着丝粒特异性组蛋白变体CENP-A的独特亚核小体的冷冻电镜分析
Genes Cells. 2025 Mar;30(2):e70016. doi: 10.1111/gtc.70016.
6
Diagnostics and immunological function of CENPN in human tumors: from pan-cancer analysis to validation in breast cancer.CENPN在人类肿瘤中的诊断及免疫功能：从泛癌分析到乳腺癌验证
Transl Cancer Res. 2025 Feb 28;14(2):881-906. doi: 10.21037/tcr-24-1291. Epub 2025 Feb 26.
7
Solution conformational differences between conventional and CENP-A nucleosomes are accentuated by reversible deformation under high pressure.在高压下的可逆变形会加剧传统核小体与着丝粒蛋白A核小体之间的溶液构象差异。
bioRxiv. 2025 Jan 21:2025.01.16.633457. doi: 10.1101/2025.01.16.633457.
8
Centromeric chromatin clearings demarcate the site of kinetochore formation.着丝粒染色质清除划定了动粒形成的位点。
Cell. 2025 Mar 6;188(5):1280-1296.e19. doi: 10.1016/j.cell.2024.12.025. Epub 2025 Jan 23.
9
High-resolution analysis of human centromeric chromatin.人类着丝粒染色质的高分辨率分析。
Life Sci Alliance. 2025 Jan 23;8(4). doi: 10.26508/lsa.202402819. Print 2025 Apr.
10
Non-nucleosomal (CENP-A/H4) - DNA complexes as a possible platform for centromere organization.非核小体（CENP-A/H4）-DNA复合物作为着丝粒组织的可能平台。
bioRxiv. 2025 Jan 1:2024.12.31.630874. doi: 10.1101/2024.12.31.630874.
Nat Cell Biol. 2019 Jun;21(6):743-754. doi: 10.1038/s41556-019-0331-4. Epub 2019 Jun 3.
4
Atomic resolution cryo-EM structure of a native-like CENP-A nucleosome aided by an antibody fragment.原子分辨率冷冻电镜结构的天然样 CENP-A 核小体，由抗体片段辅助。
Nat Commun. 2019 May 24;10(1):2301. doi: 10.1038/s41467-019-10247-4.
5
The structure of the Ctf19c/CCAN from budding yeast.酿酒酵母 Ctf19c/CCAN 的结构。
Elife. 2019 Feb 14;8:e44239. doi: 10.7554/eLife.44239.
6
The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism.CENP-A 着丝粒靶向结构域通过结构多态性促进核小体中 H4K20 的单甲基化。
Nat Commun. 2019 Feb 4;10(1):576. doi: 10.1038/s41467-019-08314-x.
7
The PRIDE database and related tools and resources in 2019: improving support for quantification data.PRIDE 数据库及相关工具和资源在 2019 年的进展：提高定量数据支持。
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450. doi: 10.1093/nar/gky1106.
8
Structural Analysis of Protein Complexes by Cross-Linking and Mass Spectrometry.通过交联和质谱法对蛋白质复合物进行结构分析
Methods Mol Biol. 2018;1764:173-183. doi: 10.1007/978-1-4939-7759-8_11.
9
MonoRes: Automatic and Accurate Estimation of Local Resolution for Electron Microscopy Maps.MonoRes：自动且精确估计电子显微镜图谱的局部分辨率。
Structure. 2018 Feb 6;26(2):337-344.e4. doi: 10.1016/j.str.2017.12.018. Epub 2018 Jan 27.
10
A systematic analysis of nucleosome core particle and nucleosome-nucleosome stacking structure.核小体核心颗粒和核小体-核小体堆积结构的系统分析。
Sci Rep. 2018 Jan 24;8(1):1543. doi: 10.1038/s41598-018-19875-0.