Flexible gates: dynamic topologies and functions for FG nucleoporins in nucleocytoplasmic transport - PubMed (original) (raw)

Review

. 2009 Dec;8(12):1814-27.

doi: 10.1128/EC.00225-09. Epub 2009 Oct 2.

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Review

Flexible gates: dynamic topologies and functions for FG nucleoporins in nucleocytoplasmic transport

Laura J Terry et al. Eukaryot Cell. 2009 Dec.

Abstract

The nuclear envelope is a physical barrier between the nucleus and cytoplasm and, as such, separates the mechanisms of transcription from translation. This compartmentalization of eukaryotic cells allows spatial regulation of gene expression; however, it also necessitates a mechanism for transport between the nucleus and cytoplasm. Macromolecular trafficking of protein and RNA occurs exclusively through nuclear pore complexes (NPCs), specialized channels spanning the nuclear envelope. A novel family of NPC proteins, the FG-nucleoporins (FG-Nups), coordinates and potentially regulates NPC translocation. The extensive repeats of phenylalanine-glycine (FG) in each FG-Nup directly bind to shuttling transport receptors moving through the NPC. In addition, FG-Nups are essential components of the nuclear permeability barrier. In this review, we discuss the structural features, cellular functions, and evolutionary conservation of the FG-Nups.

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Figures

FIG. 1.

FIG. 1.

FG-Nups are distributed throughout the NPC. (A) Schematic representation of the eightfold radial symmetry of the NPC, showing key aspects of the NPC architecture. (B) Nup subcomplexes and relative NPC substructural localization. Each box represents a biochemically or functional documented subcomplex (from studies summarized by Alber et al. [3]). S. cerevisiae FG- Nups are depicted on the left side; vertebrates are depicted on the right. The FG-Nups (colored text) are found in discrete subcomplexes and substructural locations. This includes Nups containing predominantly FG (green text), GLFG (blue text), and FXFG (red text) repeats. Select structural, non-FG-Nups are shown in black text.

FIG. 2.

FIG. 2.

Key structural and sequence features of FG-domains in S. cerevisiae. (A) The full primary amino acid sequence of S. cerevisiae Nup49 is aligned with each FG repeat in a line break to align on the left. The FG repeats (green), FXFG (red), and GLFG (blue) are further highlighted. (B) Schematic diagrams for the 11 FG-Nups in S. cerevisiae showing the distribution and type of FG repeats. Single repeats are represented by an oval. FG repeat, green; FXFG repeat, red; GLFG repeat, blue. The diagrams are adapted from Strawn et al. (157) with permission from the publisher. (C) Structural analysis of an FXFG-importin β complex gives a surface view of the FXFG peptide (red) interaction pocket. Hydrophobic residues of importin β are highlighted in yellow. (Reprinted from reference with permission from the publisher.)

FIG. 3.

FIG. 3.

Models for the mechanism of NPC selectivity and transport. Based on the different features of the respective models, the distribution and physical features of the FG domains are distinct. This is represented in structural models of both a side view (perpendicular to the NE) and top view (cross-section through center of NPC; e.g., from cytoplasm onto plane of NE). NE, black; FG domains, green; structural NPC elements, yellow; importing karyopherin transport receptor, pink; NLS-bearing cargo, blue. (A) Brownian virtual gating model (138). The center of the NPC is a narrow channel, from which FG domains extend to form an entropic barrier to transport. Transport receptors bind these FG domains, overcoming the entropic barrier. By collecting on the NPC periphery, transport complexes increase the probability that they will spontaneously move across the barrier. (B) Reduction of Dimensionality model (125, 126). FG repeats form a continuous surface along the inner face of the NPC, and transport complexes pivot along this surface. The spacer sequence between FG repeats loop outward, forming a physical barrier to diffusion of large molecules; transport complexes might transiently displace these as they move along the FG surface. (C) Selective phase-partitioning model (133, 134). Hydrophobic interactions between FG repeats form a physical meshwork with gel-like properties. Transport receptors bind and transiently dissolve the meshwork in order to translocate through the NPC.

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