真核翻译起始复合物的分子结构。
Molecular architecture of a eukaryotic translational initiation complex.
机构信息
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, CB2 0QH, United Kingdom.
Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, USA.
出版信息
Science. 2013 Nov 15;342(6160):1240585. doi: 10.1126/science.1240585. Epub 2013 Nov 7.
Abstract
The last step in eukaryotic translational initiation involves the joining of the large and small subunits of the ribosome, with initiator transfer RNA (Met-tRNA(i)(Met)) positioned over the start codon of messenger RNA in the P site. This step is catalyzed by initiation factor eIF5B. We used recent advances in cryo-electron microscopy (cryo-EM) to determine a structure of the eIF5B initiation complex to 6.6 angstrom resolution from <3% of the population, comprising just 5143 particles. The structure reveals conformational changes in eIF5B, initiator tRNA, and the ribosome that provide insights into the role of eIF5B in translational initiation. The relatively high resolution obtained from such a small fraction of a heterogeneous sample suggests a general approach for characterizing the structure of other dynamic or transient biological complexes.
摘要
真核生物翻译起始的最后一步涉及核糖体大亚基和小亚基的结合，起始转移 RNA（Met-tRNA(i)(Met)）定位于 P 位上信使 RNA 的起始密码子。这一步由起始因子 eIF5B 催化。我们利用冷冻电镜（cryo-EM）的最新进展，从<3%的群体中确定了 eIF5B 起始复合物的结构，分辨率为 6.6 埃，仅包含 5143 个颗粒。该结构揭示了 eIF5B、起始 tRNA 和核糖体的构象变化，为 eIF5B 在翻译起始中的作用提供了线索。从如此小的异质样品中获得的相对高分辨率表明了一种用于表征其他动态或瞬态生物复合物结构的通用方法。
相似文献
1
Molecular architecture of a eukaryotic translational initiation complex.真核翻译起始复合物的分子结构。
Science. 2013 Nov 15;342(6160):1240585. doi: 10.1126/science.1240585. Epub 2013 Nov 7.
2
Structural basis for the transition from translation initiation to elongation by an 80S-eIF5B complex.80S-eIF5B 复合物介导的从翻译起始到延伸的转变的结构基础。
Nat Commun. 2020 Oct 6;11(1):5003. doi: 10.1038/s41467-020-18829-3.
3
Structure of the mammalian 80S initiation complex with initiation factor 5B on HCV-IRES RNA.哺乳动物 80S 起始复合物与 HCV-IRES RNA 上起始因子 5B 的结构。
Nat Struct Mol Biol. 2014 Aug;21(8):721-7. doi: 10.1038/nsmb.2859. Epub 2014 Jul 27.
4
Long-range interdomain communications in eIF5B regulate GTP hydrolysis and translation initiation.eIF5B 中的长程结构域间通讯调节 GTP 水解和翻译起始。
Proc Natl Acad Sci U S A. 2020 Jan 21;117(3):1429-1437. doi: 10.1073/pnas.1916436117. Epub 2020 Jan 3.
5
Structural insight into the recognition of amino-acylated initiator tRNA by eIF5B in the 80S initiation complex.80S起始复合物中eIF5B对氨酰化起始tRNA识别的结构洞察。
BMC Struct Biol. 2014 Sep 17;14:20. doi: 10.1186/s12900-014-0020-2.
6
Interaction between 25S rRNA A loop and eukaryotic translation initiation factor 5B promotes subunit joining and ensures stringent AUG selection.25S rRNA A 环与真核翻译起始因子 5B 的相互作用促进亚基结合并确保严格的 AUG 选择。
Mol Cell Biol. 2013 Sep;33(18):3540-8. doi: 10.1128/MCB.00771-13. Epub 2013 Jul 8.
7
eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining.真核起始因子 5B（eIF5B）和起始因子 1A（eIF1A）使起始 tRNA 重新定位，从而允许核糖体亚基结合。
Nature. 2022 Jul;607(7917):185-190. doi: 10.1038/s41586-022-04858-z. Epub 2022 Jun 22.
8
Large-Scale Movements of IF3 and tRNA during Bacterial Translation Initiation.细菌翻译起始过程中IF3和tRNA的大规模运动
Cell. 2016 Sep 22;167(1):133-144.e13. doi: 10.1016/j.cell.2016.08.074.
9
Yeast initiator tRNA identity elements cooperate to influence multiple steps of translation initiation.酵母起始tRNA识别元件协同作用以影响翻译起始的多个步骤。
RNA. 2006 May;12(5):751-64. doi: 10.1261/rna.2263906. Epub 2006 Mar 24.
10
eIF5 and eIF5B together stimulate 48S initiation complex formation during ribosomal scanning.在核糖体扫描过程中，真核起始因子5（eIF5）和真核起始因子5B（eIF5B）共同刺激48S起始复合物的形成。
Nucleic Acids Res. 2014 Oct 29;42(19):12052-69. doi: 10.1093/nar/gku877. Epub 2014 Sep 26.
引用本文的文献
1
: .: .
3 Biotech. 2025 Feb;15(2):46. doi: 10.1007/s13205-025-04215-7. Epub 2025 Jan 19.
2
Cryo-electron microscopy in the study of virus entry and infection.低温电子显微镜在病毒进入与感染研究中的应用
Front Mol Biosci. 2024 Jul 24;11:1429180. doi: 10.3389/fmolb.2024.1429180. eCollection 2024.
3
Implication of Stm1 in the protection of eIF5A, eEF2 and tRNA through dormant ribosomes.Stm1通过休眠核糖体对真核起始因子5A、真核延伸因子2和转运RNA的保护作用。
Front Mol Biosci. 2024 Apr 18;11:1395220. doi: 10.3389/fmolb.2024.1395220. eCollection 2024.
4
The molecular basis of translation initiation and its regulation in eukaryotes.真核生物翻译起始的分子基础及其调控。
Nat Rev Mol Cell Biol. 2024 Mar;25(3):168-186. doi: 10.1038/s41580-023-00624-9. Epub 2023 Dec 5.
5
Concentration and time-dependent amyloidogenic characteristics of intrinsically disordered N-terminal region of Stm1.Stm1蛋白内在无序N端区域的浓度和时间依赖性淀粉样生成特性
Front Microbiol. 2023 Oct 19;14:1206945. doi: 10.3389/fmicb.2023.1206945. eCollection 2023.
6
Fostering discoveries in the era of exascale computing: How the next generation of supercomputers empowers computational and experimental biophysics alike.在百亿亿次级计算时代推动发现：下一代超级计算机如何为计算和实验生物物理学提供同等支持。
Biophys J. 2023 Jul 25;122(14):2833-2840. doi: 10.1016/j.bpj.2023.01.042. Epub 2023 Feb 3.
7
eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining.真核起始因子 5B（eIF5B）和起始因子 1A（eIF1A）使起始 tRNA 重新定位，从而允许核糖体亚基结合。
Nature. 2022 Jul;607(7917):185-190. doi: 10.1038/s41586-022-04858-z. Epub 2022 Jun 22.
8
Structural remodeling of ribosome associated Hsp40-Hsp70 chaperones during co-translational folding.核糖体相关 Hsp40-Hsp70 伴侣蛋白在共翻译折叠过程中的结构重塑。
Nat Commun. 2022 Jun 14;13(1):3410. doi: 10.1038/s41467-022-31127-4.
9
Role of aIF5B in archaeal translation initiation.aIF5B 在古菌翻译起始中的作用。
Nucleic Acids Res. 2022 Jun 24;50(11):6532-6548. doi: 10.1093/nar/gkac490.
10
The Structural Dynamics of Translation.翻译的结构动力学。
Annu Rev Biochem. 2022 Jun 21;91:245-267. doi: 10.1146/annurev-biochem-071921-122857. Epub 2022 Mar 14.
本文引用的文献
1
Elongation factor G bound to the ribosome in an intermediate state of translocation.结合在核糖体上处于易位中间状态的延伸因子 G。
Science. 2013 Jun 28;340(6140):1235490. doi: 10.1126/science.1235490.
2
Ribosome structures to near-atomic resolution from thirty thousand cryo-EM particles.利用三万个冷冻电镜颗粒构建出近原子分辨率的核糖体结构。
Elife. 2013 Feb 19;2:e00461. doi: 10.7554/eLife.00461.
3
RELION: implementation of a Bayesian approach to cryo-EM structure determination.RELION：贝叶斯方法在低温电子显微镜结构测定中的应用。
J Struct Biol. 2012 Dec;180(3):519-30. doi: 10.1016/j.jsb.2012.09.006. Epub 2012 Sep 19.
4
Prevention of overfitting in cryo-EM structure determination.冷冻电镜结构测定中过拟合的预防
Nat Methods. 2012 Sep;9(9):853-4. doi: 10.1038/nmeth.2115.
5
The mechanism of eukaryotic translation initiation: new insights and challenges.真核生物翻译起始的机制：新的见解和挑战。
Cold Spring Harb Perspect Biol. 2012 Oct 1;4(10):a011544. doi: 10.1101/cshperspect.a011544.
6
A translation-like cycle is a quality control checkpoint for maturing 40S ribosome subunits.翻译相似循环是成熟 40S 核糖体亚基的质量控制检查点。
Cell. 2012 Jul 6;150(1):111-21. doi: 10.1016/j.cell.2012.04.044.
7
Proofreading of pre-40S ribosome maturation by a translation initiation factor and 60S subunits.翻译起始因子和 60S 亚基对 40S 前核糖体成熟的校对作用。
Nat Struct Mol Biol. 2012 Aug;19(8):744-53. doi: 10.1038/nsmb.2308. Epub 2012 Jul 1.
8
A mechanistic overview of translation initiation in eukaryotes.真核生物翻译起始的机制概述。
Nat Struct Mol Biol. 2012 Jun 5;19(6):568-76. doi: 10.1038/nsmb.2303.
9
A Bayesian view on cryo-EM structure determination.贝叶斯视角下的冷冻电镜结构测定。
J Mol Biol. 2012 Jan 13;415(2):406-18. doi: 10.1016/j.jmb.2011.11.010. Epub 2011 Nov 12.
10
The structure of the eukaryotic ribosome at 3.0 Å resolution.真核生物核糖体的 3.0 Å 分辨率结构。
Science. 2011 Dec 16;334(6062):1524-9. doi: 10.1126/science.1212642. Epub 2011 Nov 17.
Zotero 插件