Simple fold composition and modular architecture of the nuclear pore complex
Simple fold composition and modular architecture of the nuclear pore complex
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DOI：
10.1073/pnas.0506345103
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发表时间：
2006-02-14
影响因子：
11.1
通讯作者：
Sali, A
中科院分区：
文献类型：
--
作者：
Devos, D;Dokudovskaya, S;Sali, A
核孔复合物（NPC）由大约30种不同蛋白质的多个拷贝组成[核孔蛋白（nups）]，在核膜中形成介导细胞质和细胞核之间大分子运输的通道。由于目前在实验确定的结构中可获得的nup残基< 5%，因此对NPC的详细结构知之甚少。在这里，我们使用一种结合计算和生物化学的方法来分配折叠约95%的酵母和脊椎动物nups中的残基。这些折叠分配表明所有真核NPC的结构中的组成和模块化的潜在简单性。NPC组成的简单性反映在仅存在八种折叠类型，其中三种最常见的折叠约占残基的85%。NPC结构的模块性反映在其分层和对称组织中，其将预测的nup折叠分为三组：包含跨膜螺旋和钙粘蛋白折叠的跨膜组，包含V-螺旋桨和a-螺线管折叠的中心支架组，以及主要包含FG重复和卷曲螺旋折叠的外围FG组。此外，在涂层囊泡和那些在油墨结构之间的相似性支持我们先前的假设，他们共同的进化起源于祖原衣体。NPC中预测的少量折叠类型及其内部对称性表明，NPC结构的大部分已经通过广泛的基序和基因复制从仅几种蛋白质的简单前体集合进化而来。
The nuclear pore complex (NPC) consists of multiple copies of approximate to 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 approximate to 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 approximate to 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 transmembrane group containing transmembrane helices and a cadherin fold, the central scaffold group containing V-propeller and a-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 INK 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.