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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Simple fold composition and modular architecture of the nuclear pore complex
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Simple fold composition and modular architecture of the nuclear pore complex

机译:核孔复合体的简单折叠组成和模块化结构

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The nuclear pore complex (NPC) consists of multiple copies of ≈30 different proteins [nucleoporins (nups)], forming a channel in the nuclear envelope that mediates macromolecular transport between the cytosol and the nucleus. With < 5% of the nup residues currently available in experimentally determined structures, little is known about the detailed structure of the NPC. Here, we use a combined computational and biochemical approach to assign folds for ≈95% of the residues in the yeast and vertebrate nups. These fold assignments suggest an underlying simplicity in the composition and modularity in the architecture of all eukaryotic NPCs. The simplicity in NPC composition is reflected in the presence of only eight fold types, with the three most frequent folds accounting for ≈85% of the residues. The modularity in NPC architecture is reflected in its hierarchical and symmetrical organization that partitions the predicted nup folds into three groups: the trans-membrane group containing transmembrane helices and a cad-herin fold, the central scaffold group containing β-propeller and α-solenoid folds, and the peripheral FG group containing predominantly the FG repeats and the coiled-coil fold. Moreover, similarities between structures in coated vesicles and those in the NPC support our prior hypothesis for their common evolutionary origin in a progenitor protocoatomer. The small number of predicted fold types in the NPC and their internal symmetries suggest that the bulk of the NPC structure has evolved through extensive motif and gene duplication from a simple precursor set of only a few proteins.
机译:核孔复合物(NPC)由大约30种不同蛋白质的多个副本[nuclearporins(nups)]组成,在核被膜中形成一个通道,介导细胞质和细胞核之间的大分子转运。由于目前尚有少于5%的nup残基可用于实验确定的结构,因此对NPC的详细结构了解甚少。在这里,我们使用计算和生化相结合的方法为酵母和脊椎动物小瘤中约95%的残基指定折叠倍数。这些折叠结构表明所有真核NPC的结构和模块性都具有潜在的简化性。 NPC组成的简单性反映在仅存在八种折叠类型的情况下,其中三种最常见的折叠占≈85%的残基。 NPC体系结构中的模块性体现在其层级和对称组织中,将预测的nup折叠分为三组:包含跨膜螺旋和cad-herin折叠的跨膜组,包含β-螺旋桨和α-螺鞘的中央支架组折叠,并且主要包含FG的外围FG重复和卷曲螺旋折叠。此外,包被的囊泡中的结构与NPC中的结构之间的相似性支持了我们先前的假设,即它们在祖细胞原被膜中的共同进化起源。 NPC中少数预测的折叠类型及其内部对称性表明,NPC结构的大部分已经通过仅包含少量蛋白质的简单前体集通过广泛的基序和基因复制而进化出来。

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