Nuclear export signal
Encyclopedia
A nuclear export signal (NES) is a short amino acid
sequence of 4 hydrophobic residues in a protein
that targets it for export from the cell nucleus
to the cytoplasm
through the nuclear pore
complex using nuclear transport
. It has the opposite effect of a nuclear localization signal
, which targets a protein located in the cytoplasm for import to the nucleus. The NES is recognized and bound by exportins. In silico analysis of known NESs found the most common spacing of the hydrophobic residues to be LxxxLxxLxL, where "L" is a hydrophobic residue (often leucine) and "x" is any other amino acid; the spacing of these hydrophobic residues may be explained by examination of known structures that contain an NES, as the critical residues usually lie in the same face of adjacent secondary structures within a protein, which allows them to interact with the exportin. Ribonucleic acid (RNA) are composed of nucleotides, and thus, lack the nuclear export signal to move out of the nucleus. As a result, most forms of RNA will bind to a protein molecule to form a ribonucleoprotein complex to be exported from the nucleus.
Nuclear export first begins with the binding of Ran-GTP (a G-protein) to exportin. This causes a shape change in exportin, increasing its affinity for the export cargo. Once the cargo is bound, the Ran-exportin-cargo complex moves out of the nucleus through the nuclear pore. GTPase activating protein
s (GAPs) then hydrolyze the Ran-GTP to Ran-GDP, and this causes a shape change and subsequent exportin release. Once no longer bound to Ran, the exportin molecule loses affinity for the nuclear cargo as well, and the complex falls apart. Exportin and Ran-GDP are recycled to the nucleus separately, and guanine exchange factor (GEF) in the nucleus switches the GDP for GTP on Ran.
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
sequence of 4 hydrophobic residues in a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that targets it for export from the cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
to the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
through the nuclear pore
Nuclear pore
Nuclear pores are large protein complexes that cross the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are about on average 2000 nuclear pore complexes in the nuclear envelope of a vertebrate cell, but it varies depending on cell type and the stage in...
complex using nuclear transport
Nuclear transport
The entry and exit of large molecules from the cell nucleus is tightly controlled by the nuclear pore complexes . Although small molecules can enter the nucleus without regulation, macromolecules such as RNA and proteins require association with karyopherins called importins to enter the nucleus...
. It has the opposite effect of a nuclear localization signal
Nuclear localization signal
A nuclear localization signal or sequence is an amino acid sequence which 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface. Different...
, which targets a protein located in the cytoplasm for import to the nucleus. The NES is recognized and bound by exportins. In silico analysis of known NESs found the most common spacing of the hydrophobic residues to be LxxxLxxLxL, where "L" is a hydrophobic residue (often leucine) and "x" is any other amino acid; the spacing of these hydrophobic residues may be explained by examination of known structures that contain an NES, as the critical residues usually lie in the same face of adjacent secondary structures within a protein, which allows them to interact with the exportin. Ribonucleic acid (RNA) are composed of nucleotides, and thus, lack the nuclear export signal to move out of the nucleus. As a result, most forms of RNA will bind to a protein molecule to form a ribonucleoprotein complex to be exported from the nucleus.
Nuclear export first begins with the binding of Ran-GTP (a G-protein) to exportin. This causes a shape change in exportin, increasing its affinity for the export cargo. Once the cargo is bound, the Ran-exportin-cargo complex moves out of the nucleus through the nuclear pore. GTPase activating protein
GTPase activating protein
GTPase-Activating Proteins, or GAPs, or GTPase-Accelerating Proteins are a family of regulatory proteins whose members can bind to activated G proteins and stimulate their GTPase activity, with the result of terminating the signaling event...
s (GAPs) then hydrolyze the Ran-GTP to Ran-GDP, and this causes a shape change and subsequent exportin release. Once no longer bound to Ran, the exportin molecule loses affinity for the nuclear cargo as well, and the complex falls apart. Exportin and Ran-GDP are recycled to the nucleus separately, and guanine exchange factor (GEF) in the nucleus switches the GDP for GTP on Ran.