Nuclear Location Signal

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The nuclear localization signal (also nuclear localization signal or nuclear localization sequence, English nuclear localization signal , abbreviated NLS ) is a signal sequence consisting of a few amino acids carried by proteins that are to be introduced into the cell nucleus .

properties

Cells of higher living beings ( eukaryotes ) have a cell nucleus whose nuclear membrane separates the interior of the nucleus ( caryoplasm ) from the cytoplasm . Since all proteins are produced in the cytoplasm, proteins that are needed in the cell nucleus must be introduced into it. This happens through pores in the nuclear membrane, so-called nuclear pores . Small proteins up to about 40  kDa can passively diffuse through the pores, while larger proteins have to be actively transported into the core. This happens with helper proteins, the so-called importins . Importins recognize nuclear localization signals, bind the corresponding proteins and transport them through the pore into the cell nucleus. The energy for this process is released through the hydrolysis of GTP .

The signal itself consists of a single or double short sequence, which mostly contains positively charged amino acids such as lysine and arginine . There are two different types, the classic NLS and the atypical NLS.

The classic nuclear localization signal sequence (PKKKRKV) was first described for the large T antigen of the SV40 virus . Classic NLS are further divided into one-part and two-part NLS. The two-part NLS (e.g. the sequence KR [PAATKKAGQA] KKKK in nucleoplasmin) consists of two areas of basic amino acids separated by about 10 amino acids, whereby neutral and acidic amino acids can also improve absorption. Both types of classic NLS are bound to the nuclear pore complex by binding to Importin α and its subsequent binding to Importin β.

The atypical NLS are mostly bound directly by Importin β. These include B. the M9 domain of the hnRNP A1, the repressor of transcription in yeast Matα2 (sequence KIPIK) and in U snRNPs. Ribosomal proteins have their own NLS through which they are imported into the nucleus. The PY-NLS group contains a characteristic proline - tyrosine sequence and binds to importin β2 (synonymous with transportin or karyopherin).

The replication of many viruses depends on transport processes that are mediated by nuclear localization signals. After a cell is infected, the viral genetic material usually has to be transported to the cell nucleus. This is the only place where the host cell's enzymes are located , which can replicate and transcribe the virus' genes. The virus DNA is therefore bound to viral proteins with a nuclear localization signal and is thus also imported into the cell nucleus.

There is also an adversary, core export. The nuclear export signal (NES) is a short hydrophobic leucine-rich amino acid sequence.

Individual evidence

  1. ↑ Kalderon, D. et al. (1984): A short amino acid sequence able to specify nuclear location. In: Cell. 39 (3 Pt 2): 499-509. PMID 6096007 doi: 10.1016 / 0092-8674 (84) 90457-4
  2. ↑ Dingwall C, Robbins J, Dilworth SM, Roberts B, Richardson WD: The nucleoplasmin nuclear location sequence is larger and more complex than that of SV-40 large T antigen . In: J Cell Biol . 107, No. 3, September 1988, pp. 841-9. doi : 10.1083 / jcb.107.3.841 . PMID 3417784 . PMC 2115281 (free full text).
  3. ↑ Makkerh JP, Dingwall C, Laskey RA: Comparative mutagenesis of nuclear localization signals reveals the importance of neutral and acidic amino acids . In: Curr Biol. . 6, No. 8, August 1996, pp. 1025-7. doi : 10.1016 / S0960-9822 (02) 00648-6 . PMID 8805337 .
  4. ↑ Mattaj IW, Engl Meier L: Nucleocytoplasmic transport: the soluble phase . In: Annu Rev Biochem. . 67, No. 1, 1998, pp. 265-306. doi : 10.1146 / annurev.biochem.67.1.265 . PMID 9759490 .
  5. ↑ Timmers AC, Stuger R, Schaap PJ, van 't Riet J, Raué HA: Nuclear and nucleolar localization of Saccharomyces cerevisiae ribosomal proteins S22 and S25 . In: FEBS Lett. . 452, No. 3, June 1999, pp. 335-40. doi : 10.1016 / S0014-5793 (99) 00669-9 . PMID 10386617 .
  6. ↑ Garrett RA, Douthwate SR, Matheson AT, Moore PB, Noller HF: The Ribosome: Structure, Function, Antibiotics, and Cellular Interactions . ASM Press, 2000, ISBN 978-1-55581-184-6 .
  7. ↑ Rout MP, Blobel G, Aitchison JD: A distinct nuclear import pathway used by ribosomal proteins . In: Cell . 89, No. 5, May 1997, pp. 715-25. doi : 10.1016 / S0092-8674 (00) 80254-8 . PMID 9182759 .
  8. ↑ Lee BJ, Cansizoglu AE, Süel KE, Louis TH, Zhang Z, Chook YM: Rules for nuclear localization sequence recognition by karyopherin beta 2 . In: Cell . 126, No. 3, August 2006, pp. 543-58. doi : 10.1016 / j.cell.2006.05.049 . PMID 16901787 .
  9. ↑ Yoshiyuki Matsuura: Mechanistic Insights from Structural Analyzes of Ran-GTPase-Driven Nuclear Export of Proteins and RNAs . In: Journal of Molecular Biology . 2015. doi : 10.1016 / j.jmb.2015.09.025 .