Nucleo cytoplasmic trafficking

1. General Information

d. Nuclear Transport complex (NPC)

As mentioned in the general information 1.a, NPCs are embedded in fusion sites of the inner and outer membrane of the nucleus. NPCs are large macromolecular machines of around 0.6 to 1.2 MDa, depending on the organism and way of calculation. They are composed of up to 30 different proteins. These proteins come in multiples of eight, reflected in the eightfold symmetry of the NPC.

General structure
The initial separation of nuclear pore parts in the cytoplasmic ring with filaments, the central pore embedded in the nuclear envelope and the nuclear ring with the nuclear basket attached,has been modified over the years by efforts of various structure labs using X-ray crystallography as well as electron microscopy and electron tomography.

In parallel the individual proteins commonly termed as nucleoporins (Nups) and their interactions have been elucidated at atomic level, enabling to puzzle together a detailed picture of their interactions and location in NPCs.
Figure 1 shows the proteins in the NPC and their domain organization and structural motifs.

Fig.1. Proteins involved in formation of the human nuclear pore complex. Schematic representation of human nucleoporins with their individual domains or regions assigned. Components (Top to Bottom) of the cytoplasmic filaments, Y-complex and transmembrane region, the central scaffold (adaptors and channel) and the nuclear basket. Coloring of the domains according to the color code depicted on the right. The four-letter/number code below the bars indicates available crystal structures deposited in the Protein Data Bank. Black letters indicate structures derived from Homo sapiens, gray letters indicate other organisms. The numbers in brown and gray boxes indicate the number of blades and FG-repeats, respectively. Assignments of the regions are based on the structures and as described for the human proteins in publications cited in the text or found in UniProt (

Due to structural characterization of complexes and cross-linking experiments the individual proteins could be placed in the overall structure of the NPC (Fig. 2).

Fig.2. Localisation of the Nucleoporins. (A) Structural organization of the NPC and positioning of the nucleoporins, that have been worked on in the lab. (B) Electron tomography image of the human NPC (EMDBid: 2443; Bui et al., 2013) in surface representation (beige-brown) with schematic insertion of the individual nucleoporin families, color coded as presented in Fig1. EMDB: Electron microscopy data base:

Overall, the model results in a detailed picture of the more or less rigid parts of the NPC, but misses the disordered regions of the about 30% of the proteins forming the NPS. These disordered regions contain FG repeats (grey protein regions in Fig 1. and 2.), repetitive elements of FG, GLFG, FXFG repeats connected by short 12-16 aa linker, which fill the empty channel of Figure 2.c. These regions have been shown to be an integral part of the NPCs selectivity by interacting with permissive proteins like transport receptors. Various models try to explain their function and properties. For details we refer to the literature cited below.

Further Reading
  • von Appen, A., Kosinski, J., Sparks, L., Ori, A., DiGuilio, A.L., Vollmer, B., Mackmull, M.-T., Banterle, N., Parca, L., Kastritis, P., Buczak, K., Mosalaganti, S., Hagen, W., Andres-Pons, A., Lemke, E.A., Bork, P., Antonin, W., Glavy, J.S., Bui, K.H., and Beck, M. (2015). In situ structural analysis of the human nuclear pore complex. Nature. October 1; 526(7571): 140–143. doi:10.1038/nature15381. [Abstract]

  • Bui, K.H., , von Appen, A., DiGuilio, A.L. ,Ori, A., Sparks,L., Mackmull, M-T., Bock, T., Hagen, W., Andrés-Pons, A., Glavy, J.S., Beck, M. (2013). Integrated structural analysis of the human nuclear pore complex scaffold. Cell 2013 Dec 5;155(6):1233-43.doi: 10.1016/j.cell.2013.10.055. [Abstract]

  • Akey CW, Singh D, Ouch C, Echeverria I, Nudelman I, Varberg JM, Yu Z, Fang F, Shi Y, Wang J, Salzberg D, Song K, Xu C, Gumbart JC, Suslov S, Unruh J, Jaspersen SL, Chait BT, Sali A, Fernandez-Martinez J, Ludtke SJ, Villa E, Rout MP. (2022) Comprehensive structure and functional adaptations of the yeast nuclear pore complex. Cell. Jan 20;185(2):361-378.e25. doi: 10.1016/j.cell.2021.12.015. Epub 2022 Jan 3. PMID: 34982960. [Abstract]

  • Dickmanns, A. , Kehlenbach, RH. and Fahrenkrog B. (2015) Nuclear Pore Complexes and Nucleocytoplasmic Transport: From Structure to Function to Disease. Int Rev Cell Mol Biol. 320:171-233. [Abstract]

  • Wälde, S. and Kehlenbach, R.H. (2010) The Part and the Whole: functions of nucleoporins in nucleocytoplasmic transport. Trends Cell Biol. 2010 Aug;20(8):461-9. doi: 10.1016/j.tcb.2010.05.001. [Abstract]

  • Aramburu IV, Lemke EA. (2017) Floppy but not sloppy: Interaction mechanism of FG-nucleoporins and nuclear transport receptors. Semin Cell Dev Biol. 2017 Aug;68:34-41. doi: 10.1016/j.semcdb.2017.06.026. Epub 2017 Jun 30. PMID: 28669824. [Abstract]

  • Shinkai, Y., Kuramochi, M. and Miyafusa, T. (2021) New Family Members of FG Repeat Proteins and Their Unexplored Roles During Phase Separation. Front Cell Dev Biol. 2021 Jul 12;9:708702. doi: 10.3389/fcell.2021.708702. [Abstract]