Zinc finger protein

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Representation of a zinc finger protein consisting of an α-helix and an antiparallel β-sheet structure. The zinc ion shown in green is coordinated by two histidine and two cysteine residues.
The transcription factor Zif268 (blue) contains three complexed zinc fingers and, in this illustration, binds to the DNA (orange). The coordinating amino acid residues around the zinc ions (green) are highlighted.

Zinc finger proteins are a class of nucleic acid binding proteins that have a specific protein domain : the zinc finger domain, in which a zinc ion (Zn 2+ ) is coordinated . The polypeptide chain takes through the incorporation of the zinc atom a loop-shaped structure - the so-called zinc finger - one, which specifically with the DNA or RNA can interact. They were discovered by Aaron Klug in the transcription factor IIIA from the clawed frog species Xenopus laevis .

construction

Zinc finger proteins have at least one zinc finger domain that folds around a central zinc ion (see figure). The zinc ion forms strong interactions with the sulfur, nitrogen or oxygen atoms of the amino acid residues (mostly cysteine and histidine ) due to its filled d-orbital shell . This results in a tetrahedral coordinative bond. The zinc ion is also responsible for ensuring that even relatively small sections of a polypeptide bond are stabilized in such a way that they can interact with nucleic acids. Since zinc only has one stable oxidation state, it cannot catalyze any undesired reactions within the cell. The zinc finger domain is mainly a domain that binds to DNA, so zinc finger proteins are mostly transcription factors . RNA-binding zinc finger proteins are also known. The zinc finger proteins also include receptors for steroid hormones .

In its role as a transcription factor, the loop of the protein, which contains two cysteine ​​and two histidine residues around the central Zn 2+ ion (Cys 2 His 2 zinc finger protein), binds to a specific base in the great groove of the DNA. Double helix. Zinc finger proteins can also be made up of four or six zinc-binding cysteine ​​residues (Cys 4 or Cys 6 zinc finger proteins).

The zinc finger domain always consists of a consensus sequence that can vary depending on the type of zinc finger domain.

ZAP

A special zinc finger protein is ZAP ( English zinc finger antiviral protein ). In mammals it is used to fight off viruses.

Potential application

The ability of zinc finger proteins to bind specifically to almost any DNA sequence makes specially constructed ( designed ) zinc finger proteins potential gene therapeutics for the treatment of various genetic diseases. Artificial restriction enzymes, the zinc finger nucleases , can also be produced with zinc finger domains .

Individual evidence

  1. ↑ G. Thiel, M. Lietz: Regulator of neuronal genes: zinc finger protein REST. In: Biology in Our Time . 34 (2004), pp. 96-101. doi : 10.1002 / biuz.200410244
  2. ↑ D. Voet, J. Voet, C. Pratt: Textbook of Biochemistry. 2nd Edition. Wiley-VCH, Weinheim 2010, ISBN 978-3-527-32667-9 , p. 177.
  3. ↑ Xuhua Xia: Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense , in: Molecular Biologa and Evolution, Academic Press, April 14, 2020, doi: 10.1093 / molbev / msaa094
  4. ↑ Evidence of Stray Dogs as Possible Origin of COVID-19 Pandemic , on: SciTechDaily from April 14, 2020, source: University of Ottawa
  5. ↑ M. Papwoth et al. : Designer zinc-finger proteins and their applications. In: Genes. 366 (2006), pp. 27-38. PMID 16298089
  6. ↑ J. S. Kang, J. S. Kim: Zinc finger proteins as designer transcription factors. In: J. Biol. Chem. 275 (2000), pp. 8742-8748. PMID 10722717 .
  7. ↑ WM Gomanns et al. : Engineering zinc finger protein transcription factors: the therapeutic relevance of switching endogenous gene expression on or off at command. In: J. Mol. Biol. 354 (2005), pp. 507-519. PMID 16253273

literature

  • Quinlan, K. G. R. et al. : Amplification of zinc finger gene 217 (ZNF217) and cancer: When good fingers go bad. In: Biochimica et Biophysica Acta . 1775 (2007), pp. 333-340.

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