Nuclear localization signal

Nuclear localization signal

A nuclear localizing sequence (NLS) is an amino acid sequence which acts like a 'tag' on the exposed surface of a protein. This sequence is used to target the protein to the cell nucleus through the Nuclear Pore Complex and to direct a newly synthesized protein into the nucleus via its recognition by cytosolic nuclear transport receptors. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines. Different nuclear localized proteins may share the same NLS. An NLS has the opposite function of a nuclear export signal, which targets proteins out of the nucleus.

Types of nuclear localization signals

The first NLS to be discovered is the sequence PKKKRKV in SV40 large T antigen cite journal |author=Kalderon D, Roberts BL, Richardson WD, Smith AE |title=A short amino acid sequence able to specify nuclear location |journal=Cell |volume=39 |issue=3 Pt 2 |pages=499–509 |year=1984 |pmid=6096007 |doi=10.1016/0092-8674(84)90457-4] . The NLS of nucleoplasmin, KR [PAATKKAGQA] KKKK, is the prototype of ubiquitous bipartite signal: two clusters of basic amino acids, separated by a spacer of about 10 amino acids [] . Both signals are recognized by importin α. Importin α contains a bipartite NLS itself, which is specifically recognized by importin β. The latter can be considered the actual import mediator.

Chelsky et al. proposed the consensus sequence K-K/R-X-K/R for monopartite NLSs [] . A Chelsky sequence may, therefore, be part of the downstream basic cluster of a bipartite NLS. Makkerh et al [] carried out comparative mutagenesis on the nuclear localisation signals of SV40 T-Antigen (monopartite), C-myc (monopartite) and nucleoplasmin (bipartite), and showed amino acid features common to all three. Notably the role of neutral and acidic amino acids was shown for the first time in contributing to the efficiency of the NLS cite journal |title=Comparative mutagenesis of nuclear localization signals reveals the importance of neutral and acidic amino acids |journal=Curr Biol. |volume=6 |issue=8 |pages=1025–1027 |year=1996 |pmid=8805337|doi=10.1016/S0960-9822(02)00648-6 |author=Makkerh, J] .

There are many other types of NLS, such as the acidic M9 domain of hnRNP A1, the sequence KIPIK in yeast transcription repressor Matα2, and the complex signals of U snRNPs. Most of these NLSs appear to be recognized directly by specific receptors of the importin β family without the intervention of an importin α-like protein [] .

A signal that appears to be specific for the massively produced and transported ribosomal proteins [] , [] , seems to come with a specialized set of importin β-like nuclear import receptors [] .

Mechanism of nuclear import

Proteins gain entry into the nucleus through the nuclear envelope. The nuclear envelope consist of concentric membranes, the outer and the inner membrane. These are the gateways to the nucleus. The envelope consist of pores or large nuclear complexes.

A protein translated with a NLS will bind strongly to importin (aka karyopherin), and together, the complex will move through the nuclear pore. At this point, Ran-GTP will bind to the importin-protein complex, and its binding will cause the importin to lose affinity for the protein. The protein is released, and now the Ran-GTP/importin complex will move back out of the nucleus through the nuclear pore. A GTPase activating protein (GAP) in the cytoplasm hydrolyzes the Ran-GTP to GDP, and this causes a conformational change in Ran, ultimately reducing its affinity for importin. Importin is released and Ran-GDP is recycled back to the nucleus where guanine exchange factor (GEF) exchanges its GDP back for GTP.

Nuclear export

Exporting proteins out of the nucleus is programmed by a nuclear export signal.


Additional Reading

Gorlich, D. (1997). Nuclear protein import. Current Opinion in Cell Biology, 9(3), 412-419.
C. Patrick Lusk, Gunter Blobel, and Megan C. King (2007). Highway to the inner nuclear membrane: rules for the road. Nature Reviews Molecular Cell Biology 8, 414-420 (May 2007).

Wikimedia Foundation. 2010.

Look at other dictionaries:

  • nuclear localization signal — In eukaryotes, peptide signal sequence that identifies a protein as being destined for the nucleus (see importins. Frequently the signal sequence is a collection of basic amino acids downstream of a helix breaking proline; eg. SV40 T (Pro Lys Lys …   Dictionary of molecular biology

  • Nuclear export signal — 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… …   Wikipedia

  • Nuclear localization sequence — A nuclear localization signal or sequence (NLS) 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… …   Wikipedia

  • Nuclear pore — Diagram of human cell nucleus. Nuclear pore labeled at bottom left …   Wikipedia

  • Signal peptide — A signal peptide is a short (3 60 amino acids long) peptide chain that directs the post translational transport of a protein. Signal peptides may also be called targeting signals, signal sequences, transit peptides, or localization signals. The… …   Wikipedia

  • Nuclear lamina — The nuclear lamina is a dense ( 30 to 100 nm thick) fibrillar network inside the nucleus of a eukaryotic cell. It is composed of intermediate filaments and membrane associated proteins. Besides providing mechanical support, the nuclear lamina… …   Wikipedia

  • Signal patch — A protein signal patch contains information to send a given protein to the indicated location in the cell. It is made up of amino acid residues that are distant to one another in the primary sequence, but come close to each other in the tertiary… …   Wikipedia

  • Nuclear receptor co-repressor 2 — Nuclear receptor corepressor 2 PDB rendering based on 1xc5 …   Wikipedia

  • Nuclear receptor coactivator 1 — PDB rendering based on 1oj5 …   Wikipedia

  • Nuclear receptor co-repressor 1 — Nuclear receptor corepressor 1 Rendering based on PDB 2EQR …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”

We are using cookies for the best presentation of our site. Continuing to use this site, you agree with this.