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人类GINS复合物的晶体结构。

Crystal structure of the human GINS complex.

作者信息

Choi Jung Min, Lim Hye Seong, Kim Jeong Joo, Song Ok-Kyu, Cho Yunje

机构信息

National Creative Initiatives for Structural Biology, Pohang University of Science and Technology, Pohang, Kyung Book 790-784, South Korea.

出版信息

Genes Dev. 2007 Jun 1;21(11):1316-21. doi: 10.1101/gad.1548107.

DOI:10.1101/gad.1548107
PMID:17545466
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1877744/
Abstract

The GINS complex mediates the assembly of the MCM2-7 (minichromosome maintenance) complex with proteins in a replisome progression complex. The eukaryotic GINS complex is composed of Sld5, Psf1, Psf2, and Psf3, which must be assembled for cell proliferation. We determined the crystal structure of the human GINS complex: GINS forms an elliptical shape with a small central channel. The structures of Sld5 and Psf2 resemble those of Psf1 and Psf3, respectively. In addition, the N-terminal and C-terminal domains of Sld5/Psf1 are permuted in Psf2/Psf3, which suggests that the four proteins have evolved from a common ancestor. Using a structure-based mutational analysis, we identified the functionally critical surface regions of the GINS complex.

摘要

GINS复合物介导MCM2-7(微小染色体维持)复合物与复制体前进复合物中的蛋白质组装。真核生物的GINS复合物由Sld5、Psf1、Psf2和Psf3组成,其组装对于细胞增殖是必需的。我们确定了人GINS复合物的晶体结构:GINS形成一个带有小中央通道的椭圆形。Sld5和Psf2的结构分别类似于Psf1和Psf3的结构。此外,Sld5/Psf1的N端和C端结构域在Psf2/Psf3中发生了置换,这表明这四种蛋白质是由一个共同祖先进化而来的。通过基于结构的突变分析,我们确定了GINS复合物的功能关键表面区域。

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1
Crystal structure of the human GINS complex.人类GINS复合物的晶体结构。
Genes Dev. 2007 Jun 1;21(11):1316-21. doi: 10.1101/gad.1548107.
2
The human GINS complex binds to and specifically stimulates human DNA polymerase alpha-primase.人类GINS复合物与人类DNA聚合酶α-引发酶结合并特异性地刺激该酶。
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6
Structure and function of the GINS complex, a key component of the eukaryotic replisome.真核复制体的关键组成部分 GINS 复合物的结构与功能。
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Reduced expression of GINS complex members induces hallmarks of pre-malignancy in primary untransformed human cells.GINS复合物成员的表达降低会在原代未转化的人类细胞中诱导癌前病变特征。
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Elife. 2025 Sep 8;13:RP101717. doi: 10.7554/eLife.101717.
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Structure of the Saccharolobus solfataricus GINS tetramer.嗜热栖热放线菌GINS四聚体的结构。
Acta Crystallogr F Struct Biol Commun. 2025 May 1;81(Pt 5):207-215. doi: 10.1107/S2053230X25003085. Epub 2025 Apr 16.
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GINS1 facilitates the development of lung adenocarcinoma via Wnt/β-catenin activation.GINS1通过激活Wnt/β-连环蛋白促进肺腺癌的发展。
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Zhongguo Fei Ai Za Zhi. 2024 Oct 20;27(10):735-744. doi: 10.3779/j.issn.1009-3419.2024.101.27.
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GINS2 Promotes Osteosarcoma Tumorigenesis via STAT3/MYC Axis.GINS2通过STAT3/MYC轴促进骨肉瘤肿瘤发生。
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Unwinding the Role of the CMG Helicase in Inborn Errors of Immunity.解析 CMG 解旋酶在先天性免疫缺陷中的作用。
J Clin Immunol. 2023 Jul;43(5):847-861. doi: 10.1007/s10875-023-01437-3. Epub 2023 Feb 21.
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Identification of GINS1 as a therapeutic target in the cancer patients infected with COVID-19: a bioinformatics and system biology approach.鉴定GINS1作为感染COVID-19的癌症患者的治疗靶点:一种生物信息学和系统生物学方法。
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Partial loss-of-function mutations in GINS4 lead to NK cell deficiency with neutropenia.GINS4 部分功能丧失突变导致 NK 细胞缺陷伴中性粒细胞减少症。
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本文引用的文献

1
Processing of X-ray diffraction data collected in oscillation mode.振荡模式下收集的X射线衍射数据的处理。
Methods Enzymol. 1997;276:307-26. doi: 10.1016/S0076-6879(97)76066-X.
2
The human GINS complex binds to and specifically stimulates human DNA polymerase alpha-primase.人类GINS复合物与人类DNA聚合酶α-引发酶结合并特异性地刺激该酶。
EMBO Rep. 2007 Jan;8(1):99-103. doi: 10.1038/sj.embor.7400870. Epub 2006 Dec 15.
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The DNA polymerase activity of Pol epsilon holoenzyme is required for rapid and efficient chromosomal DNA replication in Xenopus egg extracts.在非洲爪蟾卵提取物中,快速高效的染色体DNA复制需要Pol ε全酶的DNA聚合酶活性。
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4
Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase.真核生物DNA复制叉解旋酶候选物Cdc45/Mcm2-7/GINS(CMG)复合物的分离。
Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10236-10241. doi: 10.1073/pnas.0602400103. Epub 2006 Jun 23.
5
Distinct roles for Sld3 and GINS during establishment and progression of eukaryotic DNA replication forks.Sld3和GINS在真核生物DNA复制叉的建立与推进过程中的不同作用。
EMBO J. 2006 Apr 19;25(8):1753-63. doi: 10.1038/sj.emboj.7601063. Epub 2006 Apr 6.
6
GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks.GINS在真核生物DNA复制叉的复制体进展复合物中维持Cdc45与MCM的结合。
Nat Cell Biol. 2006 Apr;8(4):358-66. doi: 10.1038/ncb1382. Epub 2006 Mar 12.
7
GINS, a central nexus in the archaeal DNA replication fork.GINS是古细菌DNA复制叉中的一个核心枢纽。
EMBO Rep. 2006 May;7(5):539-45. doi: 10.1038/sj.embor.7400649. Epub 2006 Feb 17.
8
Localization of MCM2-7, Cdc45, and GINS to the site of DNA unwinding during eukaryotic DNA replication.真核生物DNA复制过程中MCM2-7、Cdc45和GINS在DNA解旋位点的定位。
Mol Cell. 2006 Feb 17;21(4):581-7. doi: 10.1016/j.molcel.2006.01.030.
9
PSF1 is essential for early embryogenesis in mice.PSF1对小鼠早期胚胎发育至关重要。
Mol Cell Biol. 2005 Dec;25(23):10528-32. doi: 10.1128/MCB.25.23.10528-10532.2005.
10
Suppressors of Bir1p (Survivin) identify roles for the chromosomal passenger protein Pic1p (INCENP) and the replication initiation factor Psf2p in chromosome segregation.Bir1p(存活素)的抑制因子确定了染色体乘客蛋白Pic1p(着丝粒蛋白)和复制起始因子Psf2p在染色体分离中的作用。
Mol Cell Biol. 2005 Oct;25(20):9000-15. doi: 10.1128/MCB.25.20.9000-9015.2005.