The crystal structure of the N-terminal region of the alpha subunit of translation initiation factor 2 (eIF2α) from Saccharomyces cerevisiae provides a view of the loop containing serine 51, the target of the eIF2α-specific kinases
The crystal structure of the N-terminal region of the alpha subunit of translation initiation factor 2 (eIF2α) from Saccharomyces cerevisiae provides a view of the loop containing serine 51, the target of the eIF2α-specific kinases
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DOI：
10.1016/j.jmb.2003.09.045
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发表时间：
2003-11-21
影响因子：
5.6
通讯作者：
Hoffman, DW
中科院分区：
文献类型：
--
作者：
Dhaliwal, S;Hoffman, DW
翻译起始因子2的阿尔法亚单位(eIF2α)是特定的蛋白激酶的靶标，它可以磷酸化保守的丝氨酸残基，作为真核生物在翻译水平调节蛋白质表达的机制的一部分。用2.5埃分辨率的X射线结晶学方法测定了酿酒酵母eIF2α的20 kDa N-末端结构。在大多数方面，该结构类似于最近解决的人类eIF2α的结构；相当长的蛋白质在其N-末端含有一个五链的反平行的β-桶，紧随其后的是一个几乎完全螺旋状的结构域。酿酒酵母eIF2pha缺乏人类和其他一些高等真核生物中存在的同源蛋白中的二硫键。有趣的是，在酿酒酵母eIF2pha的电子密度图中，可以看到一个由51-65残基组成的含有丝氨酸51的保守环；在人类蛋白质的晶体结构中没有观察到这个功能重要的环。这个环相对暴露在溶剂中，除了一些延伸的结构外，还包含两个短的3(10)螺旋。丝氨酸51位于3(10)个螺旋之一的C末端，靠近几个保守的带正电荷的残基。丝氨酸51的侧链被充分暴露，因此它的磷酸化不需要蛋白质结构的实质性改变。描述了与激酶结合和与鸟嘌呤核苷酸交换因子(EIF2B)相互作用有关的残基的结构和相对位置。(C)2003爱思唯尔有限公司。保留所有权利。
The alpha subunit of translation initiation factor 2 (eIF2alpha) is the target of specific kinases that can phosphorylate a conserved serine residue as part of a mechanism for regulating protein expression at the translational level in eukaryotes. The structure of the 20 kDa N-terminal region of eIF2alpha from Saccharomyces cerevisiae was determined by X-ray crystallography at 2.5 Angstrom resolution. In most respects, the structure is similar to that of the recently solved human eIF2alpha; the rather elongated protein contains a five-stranded antiparallel beta-barrel in its N-terminal region, followed by an almost entirely helical domain. The S. cerevisiae eIF2alpha lacks a disulfide bridge that is present in the homologous protein in humans and some of the other higher eukaryotes. Interestingly, a conserved loop consisting of residues 51-65 and containing serine 51, the putative phosphorylation site, is visible in the electron density maps of the S. cerevisiae eIF2alpha; most of this functionally important loop was not observed in the crystal structure of the human protein. This loop is relatively exposed to solvent, and contains two short 3(10) helices in addition to some extended structure. Serine 51 is located at the C-terminal end of one of the 3(10) helices and near several conserved positively charged residues. The side-chain of serine 51 is sufficiently exposed so that its phosphorylation would not necessitate a substantial change in the protein structure. The structures and relative positions of residues that have been implicated in kinase binding and in the interaction with guanine nucleotide exchange factor (eIF2B) are described. (C) 2003 Elsevier Ltd. All rights reserved.