Devos, D. et al. Simple fold composition and modular architecture of the nuclear pore complex. Proc. Natl Acad. Sci. USA 103, 2172-2177

Department of Biopharmaceutical Sciences, University of California, Mission Bay QB3, 1700 4th Street, Suite 503B, San Francisco, CA 94143-2552, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2006; 103(7):2172-7. DOI: 10.1073/pnas.0506345103
Source: PubMed


The nuclear pore complex (NPC) consists of multiple copies of approximately 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 approximately 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 approximately 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 beta-propeller and alpha-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.

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Available from: Michael P Rout
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    • "Coat nucleoporins form the inner core of nuclear pores of eukaryotes, protein supercomplexes responsible for the regulated transport of macromolecules between the nucleus and the cytoplasm. The Y-shaped Nup84/Nup107-160 subcomplex (Y-complex) forms the outer ring scaffold, is evolutionarily conserved, and is composed of certain key proteins referred to as outer ring coat nucleoporins (Y-Nups – 9 in vertebrates and 7 in yeast)12, with common structural features yet elusive sequence similarities34. While the functional capacities of coat nucleoporins are primarily connected with the nuclear pore and, in fact, despite their key role in maintaining the integrity of the outer ring, there is growing evidence for their involvement in other processes56, including mitotic spindle assembly7 and transcription regulation8. "
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    ABSTRACT: There is growing evidence for the involvement of Y-complex nucleoporins (Y-Nups) in cellular processes beyond the inner core of nuclear pores of eukaryotes. To comprehensively assess the range of possible functions of Y-Nups, we delimit their structural and functional properties by high-specificity sequence profiles and tissue-specific expression patterns. Our analysis establishes the presence of Y-Nups across eukaryotes with novel composite domain architectures, supporting new moonlighting functions in DNA repair, RNA processing, signaling and mitotic control. Y-Nups associated with a select subset of the discovered domains are found to be under tight coordinated regulation across diverse human and mouse cell types and tissues, strongly implying that they function in conjunction with the nuclear pore. Collectively, our results unearth an expanded network of Y-Nup interactions, thus supporting the emerging view of the Y-complex as a dynamic protein assembly with diverse functional roles in the cell.
    Full-text · Article · Apr 2014 · Scientific Reports
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    • "Extensive studies have identified more than 30 different nucleoporin proteins that serve as building blocks of the NPC (Rout et al., 2000; Cronshaw et al., 2002; Tamura et al., 2010). By contrast to other nuclear envelope proteins, NPC components are evolutionarily conserved between yeast, animals, and plants, indicating that these NPCs share a common progenitor (Devos et al., 2006). Based on their function in the NPC, nucleoporins are classified into two groups, including FG (phenylalanine–glycine) repeat-containing nucleoporins and scaffold nucleoporins. "
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    ABSTRACT: Plant nucleocytoplasmic transport beyond the nuclear envelope is important not only for basic cellular functions but also for growth, development, hormonal signaling, and responses to environmental stimuli. Key components of this transport system include nuclear transport receptors and nucleoporins. The functional and physical interactions between receptors and the nuclear pore in the nuclear membrane are indispensable for nucleocytoplasmic transport. Recently, several groups have reported various plant mutants that are deficient in factors involved in nucleocytoplasmic transport. Here, we summarize the current state of knowledge about nucleocytoplasmic transport in plants, and we review the plant-specific regulation and roles of this process in plants.
    Full-text · Article · Apr 2014 · Frontiers in Plant Science
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    • "Even though we found PSG and overrepresentation of some GO terms among fast evolving genes in all stages of embryogenesis (table 2), only the maternal fraction contained a network of fast evolving genes that consist of a cluster of nuclear pore (Nups) genes. Nups encode components of the nuclear pore complex that form the channels that allow the transport of proteins and RNAs from the nucleus to the cytoplasm and vice versa (Allen et al. 2000; Devos et al. 2006; Tran and Wente 2006). Interestingly, comparative genomics studies FIG. "
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    ABSTRACT: Developmental conservation among related species is a common generalization known as von Baer’s third law and implies that early stages of development are the most refractory to change. The “hourglass model” is an alternative view that proposes that middle stages are the most constrained during development. To investigate this issue, we undertook a genomic approach and provide insights into how natural selection operates on genes expressed during the first 24 h of Drosophila ontogeny in the six species of the melanogaster group for which whole genome sequences are available. Having studied the rate of evolution of more than 2,000 developmental genes, our results showed differential selective pressures at different moments of embryogenesis. In many Drosophila species, early zygotic genes evolved slower than maternal genes indicating that mid-embryogenesis is the stage most refractory to evolutionary change. Interestingly, positively selected genes were found in all embryonic stages even during the period with the highest developmental constraint, emphasizing that positive selection and negative selection are not mutually exclusive as it is often mistakenly considered. Among the fastest evolving genes, we identified a network of nucleoporins (Nups) as part of the maternal transcriptome. Specifically, the acceleration of Nups was driven by positive selection only in the more recently diverged species. Because many Nups are involved in hybrid incompatibilities between species of the Drosophila melanogaster subgroup, our results link rapid evolution of early developmental genes with reproductive isolation. In summary, our study revealed that even within functional groups of genes evolving under strong negative selection many positively selected genes could be recognized. Understanding these exceptions to the broad evolutionary conservation of early expressed developmental genes can shed light into relevant processes driving the evolution of species divergence.
    Full-text · Article · Nov 2013 · Genome Biology and Evolution
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