The Structure of the Nuclear Pore Complex (An Update)

Abstract

The nuclear pore complex (NPC) serves as the sole bidirectional gateway of macromolecules in and out of the nucleus. Owing to its size and complexity (~1,000 protein subunits, ~110 MDa in humans), the NPC has remained one of the foremost challenges for structure determination. Structural studies have now provided atomic-resolution crystal structures of most nucleoporins. The acquisition of these structures, combined with biochemical reconstitution experiments, cross-linking mass spectrometry, and cryo–electron tomography, has facilitated the determination of the near-atomic overall architecture of the symmetric core of the human, fungal, and algal NPCs. Here, we discuss the insights gained from these new advances and outstanding issues regarding NPC structure and function. The powerful combination of bottom-up and top-down approaches toward determining the structure of the NPC offers a paradigm for uncovering the architectures of other complex biological machines to near-atomic resolution.

Channel nuclear pore protein 54 directs sexual differentiation and neuronal wiring required for female reproductive behaviors inDrosophila

“…We then identified a Mi{ET1}transposon insert in the Nup54 gene, Nup54 MB03363 , that was allelic to QB62 with respect to both egg retention and reduction of receptivity after SP injection ( Figure 1B-D). Nup54 localizes to the transport channel of the megadalton nuclear pore complex that constitutes a bidirectional gateway connecting the nucleus and cytoplasm to control transport of all macromolecules [35]. The Nup54 MB03363 transposon insert leads to a truncation of the Nup54 ORF and removes the C-terminal alpha helical domain that connects Nup54 with Nup58, but leaves the core part containing the FG repeats composing the inner nuclear channel and the interaction of Nup54 with Nup62 via the alpha/beta helical region intact ( Figure 1E) [35,37,38].…”

“…Nup54 localizes to the transport channel of the megadalton nuclear pore complex that constitutes a bidirectional gateway connecting the nucleus and cytoplasm to control transport of all macromolecules [35]. The Nup54 MB03363 transposon insert leads to a truncation of the Nup54 ORF and removes the C-terminal alpha helical domain that connects Nup54 with Nup58, but leaves the core part containing the FG repeats composing the inner nuclear channel and the interaction of Nup54 with Nup62 via the alpha/beta helical region intact ( Figure 1E) [35,37,38]. Sequencing of the Nup54 QB62 allele identified a small deletion (CATTAGAGAGGAGGCGTAA) in the promoter region 186 nt upstream of the first transcribed nucleotide suggesting that this allele impacts on the expression of Nup54 ( Figure 1A), possibly only in a subset of cells, because we did not detect differences by qPCR ( Figure S1A).…”

“…Sequencing of the Nup54 QB62 allele identified a small deletion (CATTAGAGAGGAGGCGTAA) in the promoter region 186 nt upstream of the first transcribed nucleotide suggesting that this allele impacts on the expression of Nup54 ( Figure 1A), possibly only in a subset of cells, because we did not detect differences by qPCR ( Figure S1A). These two alleles represent hypomorphic mutations as channel Nups are essential genes [35].…”

“…Two essential nuclear pore proteins, Nup96 and Nup160, that are part of the outer ring of the pore and interact with each other, trigger inviability in hybrids between species through adaptive divergence in these two proteins [31][32][33][34]. The megadalton nuclear pore complex constitutes a bidirectional gateway connecting the nucleus and cytoplasm to control transport of all macromolecules [35], but how nuclear pore proteins can drive speciation is unknown.…”

Structure of the Cytoplasmic Ring of theXenopus laevisNuclear Pore Complex

“…NPC is the only route of bidirectional cargo transport between the cytoplasm and the nucleus in a eukaryotic cell. With an estimated molecular mass of about 110-125 MDa in higher eukaryotes, NPC is among the largest and most important cellular machineries [1][2][3][4][5][6] . Detailed structural information is a pre-requisite for mechanistic understanding of NPC function.…”