Nuclear pore

A nuclear pore is a part of a large complex of proteins, known as a nuclear pore complex that spans the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are approximately 1,000 nuclear pore complexes (NPCs) in the nuclear envelope of a vertebrate cell, but it varies depending on cell type and the stage in the life cycle. The human nuclear pore complex (hNPC) is a 110 MDa structure. The proteins that make up the nuclear pore complex are known as nucleoporins; each NPC contains at least 456 individual protein molecules and is composed of 34 distinct nucleoporin proteins.About half of the nucleoporins typically contain solenoid protein domains—either an alpha solenoid or a beta-propeller fold, or in some cases both as separate structural domains. The other half show structural characteristics typical of 'natively unfolded' or intrinsically disordered proteins, i.e. they are highly flexible proteins that lack ordered tertiary structure. These disordered proteins are the FG nucleoporins, so called because their amino-acid sequence contains many phenylalanine—glycine repeats. A nuclear pore is a part of a large complex of proteins, known as a nuclear pore complex that spans the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are approximately 1,000 nuclear pore complexes (NPCs) in the nuclear envelope of a vertebrate cell, but it varies depending on cell type and the stage in the life cycle. The human nuclear pore complex (hNPC) is a 110 MDa structure. The proteins that make up the nuclear pore complex are known as nucleoporins; each NPC contains at least 456 individual protein molecules and is composed of 34 distinct nucleoporin proteins.About half of the nucleoporins typically contain solenoid protein domains—either an alpha solenoid or a beta-propeller fold, or in some cases both as separate structural domains. The other half show structural characteristics typical of 'natively unfolded' or intrinsically disordered proteins, i.e. they are highly flexible proteins that lack ordered tertiary structure. These disordered proteins are the FG nucleoporins, so called because their amino-acid sequence contains many phenylalanine—glycine repeats. Nuclear pore complexes allow the transport of molecules across the nuclear envelope. This transport includes RNA and ribosomal proteins moving from nucleus to the cytoplasm and proteins (such as DNA polymerase and lamins), carbohydrates, signaling molecules and lipids moving into the nucleus. It is notable that the nuclear pore complex (NPC) can actively conduct 1000 translocations per complex per second. Although smaller molecules simply diffuse through the pores, larger molecules may be recognized by specific signal sequences and then be diffused with the help of nucleoporins into or out of the nucleus. It has been recently shown that these nucleoporins have specific evolutionary conserved features encoded in their sequences that provide insight into how they regulate the transport of molecules through the nuclear pore. Nucleoporin-mediated transport is not directly energy requiring, but depends on concentration gradients associated with the RAN cycle. Each of the eight protein subunits surrounding the actual pore (the outer ring) projects a spoke-shaped protein over the pore channel. The center of the pore often appears to contain a plug-like structure. It is yet unknown whether this corresponds to an actual plug or is merely cargo caught in transit. The entire nuclear pore complex has a diameter of about 120 nanometers in vertebrates. The diameter of the channel ranges from 5.2 nanometers in humans to 10.7 nm in the frog Xenopus laevis, with a depth of roughly 45 nm. mRNA, which is single-stranded, has a thickness of about 0.5 to 1 nm. The molecular mass of the mammalian NPC is about 124 megadaltons (MDa) and it contains approximately 30 different protein components, each in multiple copies. In contrast, the yeast Saccharomyces cerevisiae is smaller, with a mass of only 66 MDa. Small particles (< ~30-60 kDa) are able to pass through the nuclear pore complex by passive diffusion. Larger particles are also able to diffuse passively through the large diameter of the pore, at rates that decrease gradually with molecular weight. Efficient passage through the complex requires several protein factors, and in particular, nuclear transport receptors that bind to cargo molecules and mediate their translocation across the NPC, either into the nucleus (importins) or out of it (exportins). The largest family of nuclear transport receptors are karyopherins, which includes dozens of both importins and exportins; this family is further subdivided to the karyopherin-α and the karyopherin-β subfamilies. Other nuclear transport receptors include NTF2 and some NTF2-like proteins.