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MEHMO syndrome mutation EIF2S3-I259M impairs initiator Met-tRNAiMet binding to eukaryotic translation initiation factor eIF2.MEHMO 综合征突变 EIF2S3-I259M 损害起始 Met-tRNAiMet 与真核翻译起始因子 eIF2 的结合。
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Fidelity of start codon selection influences 3-amino-1,2,4-triazole sensitivity in GTPase activating protein function defective eIF5.起始密码子选择的保真度影响GTP酶激活蛋白功能缺陷的eIF5中3-氨基-1,2,4-三唑的敏感性。
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本文引用的文献

1
Structure of an archaeal heterotrimeric initiation factor 2 reveals a nucleotide state between the GTP and the GDP states.古细菌异源三聚体起始因子2的结构揭示了一种介于GTP和GDP状态之间的核苷酸状态。
Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18445-50. doi: 10.1073/pnas.0706784104. Epub 2007 Nov 13.
2
Dissociation of eIF1 from the 40S ribosomal subunit is a key step in start codon selection in vivo.真核起始因子1（eIF1）从40S核糖体亚基上解离是体内起始密码子选择的关键步骤。
Genes Dev. 2007 May 15;21(10):1217-30. doi: 10.1101/gad.1528307.
3
The eukaryotic translation initiation factors eIF1 and eIF1A induce an open conformation of the 40S ribosome.真核生物翻译起始因子eIF1和eIF1A诱导40S核糖体形成开放构象。
Mol Cell. 2007 Apr 13;26(1):41-50. doi: 10.1016/j.molcel.2007.03.018.
4
Intragenic suppressor mutations restore GTPase and translation functions of a eukaryotic initiation factor 5B switch II mutant.基因内抑制突变可恢复真核起始因子5B开关II突变体的GTP酶和翻译功能。
Mol Cell Biol. 2007 Mar;27(5):1677-85. doi: 10.1128/MCB.01258-06. Epub 2006 Dec 22.
5
Direct binding of translation initiation factor eIF2gamma-G domain to its GTPase-activating and GDP-GTP exchange factors eIF5 and eIF2B epsilon.翻译起始因子eIF2γ-G结构域与其GTP酶激活因子及GDP-GTP交换因子eIF5和eIF2Bε的直接结合。
J Biol Chem. 2006 May 5;281(18):12636-44. doi: 10.1074/jbc.M511700200. Epub 2006 Mar 7.
6
Pi release from eIF2, not GTP hydrolysis, is the step controlled by start-site selection during eukaryotic translation initiation.真核生物翻译起始过程中，起始位点选择所控制的步骤是eIF2上Pi的释放，而非GTP水解。
Mol Cell. 2005 Oct 28;20(2):251-62. doi: 10.1016/j.molcel.2005.09.008.
7
Translational regulation of GCN4 and the general amino acid control of yeast.GCN4的翻译调控与酵母的一般氨基酸控制
Annu Rev Microbiol. 2005;59:407-50. doi: 10.1146/annurev.micro.59.031805.133833.
8
A conformational change in the eukaryotic translation preinitiation complex and release of eIF1 signal recognition of the start codon.真核生物翻译起始前复合物的构象变化以及真核起始因子1（eIF1）的释放标志着起始密码子的识别。
Mol Cell. 2005 Jan 21;17(2):265-75. doi: 10.1016/j.molcel.2004.11.051.
9
Release of initiation factors from 48S complexes during ribosomal subunit joining and the link between establishment of codon-anticodon base-pairing and hydrolysis of eIF2-bound GTP.核糖体亚基结合过程中起始因子从48S复合物的释放以及密码子-反密码子碱基配对的建立与eIF2结合的GTP水解之间的联系。
Genes Dev. 2004 Dec 15;18(24):3078-93. doi: 10.1101/gad.1255704.
10
Interactions of eukaryotic translation initiation factor 3 (eIF3) subunit NIP1/c with eIF1 and eIF5 promote preinitiation complex assembly and regulate start codon selection.真核生物翻译起始因子3（eIF3）亚基NIP1/c与eIF1和eIF5的相互作用促进起始前复合物组装并调节起始密码子选择。
Mol Cell Biol. 2004 Nov;24(21):9437-55. doi: 10.1128/MCB.24.21.9437-9455.2004.

翻译起始因子2γ突变体改变起始密码子选择，与甲硫氨酰-tRNA结合无关。

Translation initiation factor 2gamma mutant alters start codon selection independent of Met-tRNA binding.

作者信息

Alone Pankaj V, Cao Chune, Dever Thomas E

机构信息

Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Mol Cell Biol. 2008 Nov;28(22):6877-88. doi: 10.1128/MCB.01147-08. Epub 2008 Sep 15.

DOI:10.1128/MCB.01147-08
PMID:18794367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2573310/
Abstract

Selection of the AUG start codon for translation in eukaryotes is governed by codon-anticodon interactions between the initiator Met-tRNA(i)(Met) and the mRNA. Translation initiation factor 2 (eIF2) binds Met-tRNA(i)(Met) to the 40S ribosomal subunit, and previous studies identified Sui(-) mutations in eIF2 that enhanced initiation from a noncanonical UUG codon, presumably by impairing Met-tRNA(i)(Met) binding. Consistently, an eIF2gamma-N135D GTP-binding domain mutation impairs Met-tRNA(i)(Met) binding and causes a Sui(-) phenotype. Intragenic A208V and A382V suppressor mutations restore Met-tRNA(i)(Met) binding affinity and cell growth; however, only A208V suppresses the Sui(-) phenotype associated with the eIF2gamma-N135D mutation. An eIF2gamma-A219T mutation impairs Met-tRNA(i)(Met) binding but unexpectedly enhances the fidelity of initiation, suppressing the Sui(-) phenotype associated with the eIF2gamma-N135D,A382V mutant. Overexpression of eIF1, which is thought to monitor codon-anticodon interactions during translation initiation, likewise suppresses the Sui(-) phenotype of the eIF2gamma mutants. We propose that structural alterations in eIF2gamma subtly alter the conformation of Met-tRNA(i)(Met) on the 40S subunit and thereby affect the fidelity of start codon recognition independent of Met-tRNA(i)(Met) binding affinity.

摘要

真核生物中翻译起始密码子AUG的选择由起始甲硫氨酰 - tRNA(i)(Met)与mRNA之间的密码子 - 反密码子相互作用决定。翻译起始因子2（eIF2）将甲硫氨酰 - tRNA(i)(Met)与40S核糖体亚基结合，先前的研究在eIF2中鉴定出Sui(-)突变，该突变增强了从非规范UUG密码子的起始，推测是通过损害甲硫氨酰 - tRNA(i)(Met)的结合。一致地，eIF2γ - N135D GTP结合结构域突变损害甲硫氨酰 - tRNA(i)(Met)的结合并导致Sui(-)表型。基因内的A208V和A382V抑制突变恢复了甲硫氨酰 - tRNA(i)(Met)的结合亲和力和细胞生长；然而，只有A208V抑制与eIF2γ - N135D突变相关的Sui(-)表型。eIF2γ - A219T突变损害甲硫氨酰 - tRNA(i)(Met)的结合，但出乎意料地增强了起始的保真度，抑制了与eIF2γ - N135D、A382V突变体相关的Sui(-)表型。eIF1的过表达被认为在翻译起始期间监测密码子 - 反密码子相互作用，同样抑制了eIF2γ突变体的Sui(-)表型。我们提出，eIF2γ中的结构改变会微妙地改变40S亚基上甲硫氨酰 - tRNA(i)(Met)的构象，从而独立于甲硫氨酰 - tRNA(i)(Met)结合亲和力影响起始密码子识别的保真度。