CENP-A-组蛋白 H4 异二聚体与伴侣蛋白 HJURP 复合物的结构。
Structure of a CENP-A-histone H4 heterodimer in complex with chaperone HJURP.
机构信息
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
出版信息
Genes Dev. 2011 May 1;25(9):901-6. doi: 10.1101/gad.2045111. Epub 2011 Apr 8.
Abstract
In higher eukaryotes, the centromere is epigenetically specified by the histone H3 variant Centromere Protein-A (CENP-A). Deposition of CENP-A to the centromere requires histone chaperone HJURP (Holliday junction recognition protein). The crystal structure of an HJURP-CENP-A-histone H4 complex shows that HJURP binds a CENP-A-H4 heterodimer. The C-terminal β-sheet domain of HJURP caps the DNA-binding region of the histone heterodimer, preventing it from spontaneous association with DNA. Our analysis also revealed a novel site in CENP-A that distinguishes it from histone H3 in its ability to bind HJURP. These findings provide key information for specific recognition of CENP-A and mechanistic insights into the process of centromeric chromatin assembly.
摘要
在高等真核生物中，着丝粒通过组蛋白 H3 变体着丝粒蛋白 A (CENP-A) 被表观遗传指定。CENP-A 向着丝粒的沉积需要组蛋白伴侣 HJURP（霍利迪接头识别蛋白）。HJURP-CENP-A-组蛋白 H4 复合物的晶体结构表明，HJURP 结合 CENP-A-H4 异二聚体。HJURP 的 C 末端 β-折叠结构域覆盖组蛋白异二聚体的 DNA 结合区域，防止其自发与 DNA 结合。我们的分析还揭示了 CENP-A 中的一个新位点，该位点能够区分其与组蛋白 H3 的结合能力，从而区分 CENP-A。这些发现为 CENP-A 的特异性识别提供了关键信息，并深入了解了着丝粒染色质组装的机制。
相似文献
1
Structure of a CENP-A-histone H4 heterodimer in complex with chaperone HJURP.
Genes Dev. 2011 May 1;25(9):901-6. doi: 10.1101/gad.2045111. Epub 2011 Apr 8.
2
HJURP binds CENP-A via a highly conserved N-terminal domain and mediates its deposition at centromeres.
Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1349-54. doi: 10.1073/pnas.0913709107. Epub 2010 Jan 6.
3
Dimerization of the CENP-A assembly factor HJURP is required for centromeric nucleosome deposition.
EMBO J. 2013 Jul 31;32(15):2113-24. doi: 10.1038/emboj.2013.142. Epub 2013 Jun 14.
4
HJURP uses distinct CENP-A surfaces to recognize and to stabilize CENP-A/histone H4 for centromere assembly.
Dev Cell. 2012 Apr 17;22(4):749-62. doi: 10.1016/j.devcel.2012.02.001. Epub 2012 Mar 8.
5
Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP.
Cell. 2009 May 1;137(3):472-84. doi: 10.1016/j.cell.2009.02.039.
6
Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing.
Nat Commun. 2019 Sep 6;10(1):4046. doi: 10.1038/s41467-019-12019-6.
7
Structural basis for recognition of centromere histone variant CenH3 by the chaperone Scm3.
Nature. 2011 Apr 14;472(7342):234-7. doi: 10.1038/nature09854. Epub 2011 Mar 16.
8
Identification of the Post-translational Modifications Present in Centromeric Chromatin.
Mol Cell Proteomics. 2016 Mar;15(3):918-31. doi: 10.1074/mcp.M115.053710. Epub 2015 Dec 18.
9
The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres.
Nature. 2010 Sep 16;467(7313):347-51. doi: 10.1038/nature09323. Epub 2010 Aug 25.
10
Comparison between the CENP-A and histone H3 structures in nucleosomes.
Nucleus. 2012 Jan-Feb;3(1):6-11. doi: 10.4161/nucl.18372.
引用本文的文献
1
Maternal CENP-C restores centromere symmetry in mammalian zygotes to ensure proper chromosome segregation.
bioRxiv. 2025 Jul 28:2025.07.23.666394. doi: 10.1101/2025.07.23.666394.
2
A predictive chromatin architecture nexus regulates transcription and DNA damage repair.
J Biol Chem. 2025 Mar;301(3):108300. doi: 10.1016/j.jbc.2025.108300. Epub 2025 Feb 11.
3
Non-nucleosomal (CENP-A/H4) - DNA complexes as a possible platform for centromere organization.
bioRxiv. 2025 Jan 1:2024.12.31.630874. doi: 10.1101/2024.12.31.630874.
4
Structural basis for Mis18 complex assembly and its implications for centromere maintenance.
EMBO Rep. 2024 Aug;25(8):3348-3372. doi: 10.1038/s44319-024-00183-w. Epub 2024 Jul 1.
5
Centromere structure and function: lessons from Drosophila.
Genetics. 2023 Dec 6;225(4). doi: 10.1093/genetics/iyad170.
6
The cell-cycle choreography of H3 variants shapes the genome.
Mol Cell. 2023 Nov 2;83(21):3773-3786. doi: 10.1016/j.molcel.2023.08.030. Epub 2023 Sep 20.
7
Advances in holliday junction recognition protein (HJURP): Structure, molecular functions, and roles in cancer.
Front Cell Dev Biol. 2023 Mar 21;11:1106638. doi: 10.3389/fcell.2023.1106638. eCollection 2023.
8
CENP-I directly targets centromeric DNA to support CENP-A deposition and centromere maintenance.
Proc Natl Acad Sci U S A. 2023 Mar 14;120(11):e2219170120. doi: 10.1073/pnas.2219170120. Epub 2023 Mar 8.
9
DAXX adds a de novo H3.3K9me3 deposition pathway to the histone chaperone network.
Mol Cell. 2023 Apr 6;83(7):1075-1092.e9. doi: 10.1016/j.molcel.2023.02.009. Epub 2023 Mar 2.
10
Centromere Chromatin Dynamics at a Glance.
Epigenomes. 2022 Nov 3;6(4):39. doi: 10.3390/epigenomes6040039.
本文引用的文献
1
Processing of X-ray diffraction data collected in oscillation mode.
Methods Enzymol. 1997;276:307-26. doi: 10.1016/S0076-6879(97)76066-X.
2
Epigenetic centromere propagation and the nature of CENP-a nucleosomes.
Cell. 2011 Feb 18;144(4):471-9. doi: 10.1016/j.cell.2011.02.002.
3
Tetrameric organization of vertebrate centromeric nucleosomes.
Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20317-22. doi: 10.1073/pnas.1009563107. Epub 2010 Nov 8.
4
Epigenetic inheritance of centromeres.
Cold Spring Harb Symp Quant Biol. 2010;75:51-60. doi: 10.1101/sqb.2010.75.001. Epub 2010 Nov 3.
5
The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres.
Nature. 2010 Sep 16;467(7313):347-51. doi: 10.1038/nature09323. Epub 2010 Aug 25.
6
The histone chaperone Nap1 promotes nucleosome assembly by eliminating nonnucleosomal histone DNA interactions.
Mol Cell. 2010 Mar 26;37(6):834-42. doi: 10.1016/j.molcel.2010.01.037.
7
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21. doi: 10.1107/S0907444909052925. Epub 2010 Jan 22.
8
HJURP binds CENP-A via a highly conserved N-terminal domain and mediates its deposition at centromeres.
Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1349-54. doi: 10.1073/pnas.0913709107. Epub 2010 Jan 6.
9
Common ancestry of the CENP-A chaperones Scm3 and HJURP.
Cell. 2009 Jun 26;137(7):1173-4. doi: 10.1016/j.cell.2009.06.010.
10
HJURP is a cell-cycle-dependent maintenance and deposition factor of CENP-A at centromeres.
Cell. 2009 May 1;137(3):485-97. doi: 10.1016/j.cell.2009.02.040.
Zotero 插件