Structural Biochemistry/Membrane Proteins/Nuclear Pore Complex
Macromolecules must move between the nucleus and cytoplasm often in eukaryotic cells because replication and transcription happens in the nucleus and translation happens in the cytoplasm. The nuclear envelope separates the nucleoplasm (that has the genetic material) from the cytoplasm; the RNA molecules that are made in the nucleus must be translated to proteins in the cytoplasm. These macromolecules move through the nuclear envelope by way nuclear pore complexes (NPC).
The nuclear pore complex was discovered in 1950 and has been studied extensively by electron microscopy. Nuclear pore complexes are the openings that macromolecules use to cross from the nucleus to the cytoplasm and vice versa. NPCs are pores in the nuclear envelope and are a part of aqueous transport channels that participate in the transport of macromolecules between the cytoplasm and nucleus.
The nuclear pore complex is made of thirty different proteins known as nucleoporins; there are about 500-1000 proteins in the NPC because the NPC has internal symmetry and each nucleoporin repeats many times. Nucleoporins are made from α- helical regions, β-propellers, and phenylalanine-glycine (FG) repeats.
Electron microscopy revealed that the nuclear pore complex had a donut shaped core and is covered with cytoplasmic filaments and has a nuclear basket. It is unfeasible to use X-Ray crystallography to study the structure of the NPC because of size and flexibility of the complex and because it is very difficult to get a large amount of the pure complex in order to form a crystal.
The function of the nuclear pore complex, as stated above, is to help transport macromolecules back and forth between the nucleus and the cytoplasm. In addition, the nuclear pore complex also serves as a barrier between the cytoplasm and nucleus to prevent harm to genetic material housed in the nucleus. Macromolecules move through the NPC through diffusion channels (up to a size of about 40 kilodaltons), the diffusion barrier is made by spreading nucleoporins that have many FG repeats. FG repeats also serve an important role in the NPC; they act as a docking zone for transport receptors (known as karyopherins) that move molecules between the NPC. For molecules to move through the NPC, they have short localization sequences for import, and nuclear export sequences for export.
The nuclear pore complex has roles outside of nucleocytoplasmic transport between the nucleus and cytoplasm. The NPC is also involved in chromatin organization, gene expression regulation, DNA repair, and many other functions.
Defects in the nuclear pore complex lead to many diseases because it is integral to cellular structure. These diseases include hematological neoplasms, heart arrhythmia, primary biliary cirrhosis, and others.
Hoelz, Andre, Erik Debler, and Gunter Blobel. "The Structure of the Nuclear Pore Complex." Annual Review of Biochemistry. (2011): 35. Web. 12 Nov. 2011. <http://www.annualreviews.org/doi/pdf/10.1146/annurev-biochem-060109-151030>.
Tim Isgro, and Lingling Miao. NPC. 2006. Graphic. Theoretical and Computational Biophysics Group, Urbana-Champaign.