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, 2012). Macromolecules traffic between the nucleus and cytoplasm through these pores that fuse the inner and outer nuclear envelope. Protein complexes known as the nuclear pore complex (NPC) are integrated within the nuclear pores and act as gates that restrict the diffusion of larger biomolecules across the nuclear envelope. With an approximate mass of 125 MDa, the NPC is one of the largest and most complex assemblages of proteins in the eukaryotic cell and is composed of approximately 30 different nucleoporin (Nup) proteins, with ~500�C1000 individual Nups comprising a single NPC (Reichelt et al., 1990; Cronshaw et al., 2002; Hoelz et al., 2011). The NPC is a dynamic and modular Veliparib clinical trial structure with eight-fold rotational symmetry and can be divided into three recognizable ring-like structures surrounding the central channel of the nuclear pore: the cytoplasmic ring, the central spoke ring, and the nuclear ring (which make up the symmetrical portion of NPC) (Frenkiel-Krispin et al., 2010). Attached to the cytoplasmic ring and nuclear ring are 8 proteinaceous filaments which extend into the cytoplasm and nucleus, respectively, with the nuclear filaments converging to form the nuclear basket (Cautain et al., 2015). These extended structures, together, make up the asymmetric portion of the NPC. Nups are categorized as transmembrane, barrier, or scaffold Nups based upon location within the NPC, amino acid sequence motifs, and structure (Grossman et al., 2012). Transmembrane Nups anchor the NPC to the nuclear envelope pores, barrier Nups facilitate active transport of cargoes, and scaffold Nups link the transmembrane Nups to the barrier Nups, providing the structural framework of the NPC (Figure ?(Figure11). Figure 1 The nuclear pore complex. The cytoplasmic (dark blue), central spoke (light blue), and nuclear ring (chartreuse) structures constitute the symmetric portion of the nuclear pore complex (NPC) that surrounds the central channel. The asymmetric portion of ... Barrier Nups contain repeated phenylalanine-glycine-rich (FG) sequences that form intrinsically disordered motifs and act as the major impediment to free diffusion through the main channel of the NPC (Cautain et al., 2015). Concomitantly, these FG-Nups provide the only route for active transport of cargo biomolecules between the cytoplasm and nucleus by providing binding sites for nuclear transport receptors, within the NPC, through multiple low-affinity interactions (Ben-Efraim and Gerace, 2001; Ribbeck and G?rlich, 2001). The translocation of complexes through the NPC is energy-independent as GTP hydrolysis is required only as a final step in the transport process (Schwoebel et al., 1998).