GTP binding to translation factor eIF2B stimulates its guanine nucleotide exchange activity.
GTP binding to translation factor eIF2B stimulates its guanine nucleotide exchange activity.
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DOI：
10.1016/j.isci.2021.103454
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发表时间：
2021-12-17
期刊：
影响因子：
5.8
通讯作者：
Pavitt GD
中科院分区：
文献类型：
--
作者：
Kershaw CJ;Jennings MD;Cortopassi F;Guaita M;Al-Ghafli H;Pavitt GD
eIF 2B是真核生物细胞质蛋白质合成起始所需的鸟嘌呤核苷酸交换因子（GEF），并在整合应激反应（ISR）中进行调节。它激活其伴侣因子eIF 2，从而促进翻译起始。在这里，我们提供的证据，通过生物化学和遗传学的方法，eIF 2B可以直接结合到GTP，这可以提高其对eIF 2-GDP的GEF活性在体外的速度。GTP与eIF 2B γ和ε亚基的亚复合物结合。eIF 2B γ氨基端结构域与结合特异性核苷酸的己糖磷酸焦磷酸化酶具有结构同源性，eIF 2B γ中的K66 R突变在一系列功能测定中对鸟嘌呤或GTP特别敏感。综上所述，我们的数据表明eIF 2B γ可能作为嘌呤核苷酸可用性的传感器，从而调节eIF 2B活性和蛋白质合成，以响应细胞核苷酸水平的波动。eIF 2B是eIF 2翻译及其控制的GDP交换因子，结合GTP GTP GTP结合增强eIF 2B体外GEF活性对eIF 2-GDP的速率酵母中的K66 R突变eIF 2B γ对体内鸟嘌呤或体外GTP敏感eIF 2B可作为嘌呤核苷酸可用性的传感器生物科学;分子生物学;细胞生物学;生物力学
eIF2B is the guanine nucleotide exchange factor (GEF) required for cytoplasmic protein synthesis initiation in eukaryotes and its regulation within the integrated stress response (ISR). It activates its partner factor eIF2, thereby promoting translation initiation. Here we provide evidence through biochemical and genetic approaches that eIF2B can bind directly to GTP and this can enhance its rate of GEF activity toward eIF2–GDP in vitro. GTP binds to a subcomplex of the eIF2Bγ and ε subunits. The eIF2Bγ amino-terminal domain shares structural homology with hexose sugar phosphate pyrophosphorylase enzymes that bind specific nucleotides. A K66R mutation in eIF2Bγ is especially sensitive to guanine or GTP in a range of functional assays. Taken together, our data suggest eIF2Bγ may act as a sensor of purine nucleotide availability and thus modulate eIF2B activity and protein synthesis in response to fluctuations in cellular nucleotide levels. eIF2B, the GDP exchange factor for eIF2 in translation and its control, binds GTP GTP binding enhances the rate of eIF2B GEF activity toward eIF2–GDP in vitro A K66R mutation in yeast eIF2Bγ is sensitive to guanine in vivo or GTP in vitro eIF2B may act as a sensor of purine nucleotide availability Biological sciences; Molecular biology; Cell biology; Biomechanics
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影响因子：
14.9
作者：
Jennings MD;Kershaw CJ;White C;Hoyle D;Richardson JP;Costello JL;Donaldson IJ;Zhou Y;Pavitt GD
通讯作者：
Pavitt GD
影响因子：
8
作者：
KOONIN, EV
通讯作者：
KOONIN, EV
影响因子：
5.3
作者：
BUSHMAN, JL;ASURU, AI;HINNEBUSCH, AG
通讯作者：
HINNEBUSCH, AG
影响因子：
16
作者：
Llácer JL;Hussain T;Marler L;Aitken CE;Thakur A;Lorsch JR;Hinnebusch AG;Ramakrishnan V
通讯作者：
Ramakrishnan V
影响因子：
11.4
作者：
Gomez, E;Mohammad, SS;Pavitt, GD
通讯作者：
Pavitt, GD