Assembly of eIF3 Mediated by Mutually Dependent Subunit Insertion.
Assembly of eIF3 Mediated by Mutually Dependent Subunit Insertion.
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DOI：
10.1016/j.str.2016.02.024
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发表时间：
2016-06-07
期刊：
影响因子：
--
通讯作者：
Cate JH
中科院分区：
文献类型：
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作者：
Smith MD;Arake-Tacca L;Nitido A;Montabana E;Park A;Cate JH
真核起始因子3（eIF 3）是一种参与翻译起始的多蛋白复合物，由12个紧密相关的亚基组成。虽然eIF 3的总体结构是已知的，但其组装机制以及许多癌症中eIF 3亚基表达失调的结构后果在很大程度上尚不清楚。在这里，我们表明，亚基eIF 3组装成eIF 3在一个相互依赖的方式。eIF 3的组装主要由螺旋束的形成控制，所述螺旋束由从八个亚基中的PCI-MPN结构域C-末端延伸的螺旋组成。我们提出，虽然类人eIF 3的最小亚复合物在细胞中的翻译起始功能由亚基a，B，c，f，g，i和m组成，许多其他eIF 3亚复合物存在的亚基过表达或低表达的情况下。因此，由于亚基表达失调而形成或“释放”的eIF 3亚复合物可能是促成eIF 3相关癌症的决定性因素。
Eukaryotic initiation factor 3 (eIF3), an essential multi-protein complex involved in translation initiation, is composed of 12 tightly associated subunits in humans. While the overall structure of eIF3 is known, the mechanism of its assembly and structural consequences of dysregulation of eIF3 subunit expression seen in many cancers is largely unknown. Here we show that subunits in eIF3 assemble into eIF3 in an interdependent manner. Assembly of eIF3 is governed primarily by formation of a helical bundle, composed of helices extending C-terminally from PCI-MPN domains in eight subunits. We propose that, while the minimal subcomplex of human-like eIF3 functional for translation initiation in cells consists of subunits a, b, c, f, g, i, and m, numerous other eIF3 subcomplexes exist under circumstances of subunit over- or underexpression. Thus, eIF3 subcomplexes formed or “released” due to dysregulated subunit expression may be determining factors contributing to eIF3-related cancers.