Zinc‐finger Genes


Zinc‐fingers (ZnFs) are small protein domains stabilized by one or more zinc ions. ZnF proteins are abundant in higher eukaryotes, and many contain multiple ZnF domains. Initially thought to be peculiar to transcription factors and other deoxyribonucleic acid (DNA)‐binding proteins, these domains can also interact with other proteins, ribonucleic acid (RNA) and lipids, implicating them in a mélange of biological processes.

Keywords: zinc‐finger; DNA‐binding protein; protein–protein interactions; cysteine; histidine

Figure 1.

Representatives of major ZnF classes. (a) Classical C2H2 domain from Xfin, PDB 1znf. (b) GATA‐1 NF treble clef, PDB 1y0j. (c) Single LIM domain from LM04, PDB 1rut. (d) Crossbraced RING finger of Equine herpes virus type 1, PDB 1chc. (e) Zinc ribbon of Npl4, PDB 1nj3. Side chains of liganding residues are shown in yellow, with zinc ions coloured magenta.

Figure 2.

Unusual zinc‐fingers. (a) CBP TAZ1 coordinates three zinc ions, PDB 1u2n. (b) DNA‐interacting Zn2/Cys6 domain of yeast PPR1, PDB 1pyi. (c) Interdomain loop of MFP2b with separated HCCC motif, PDB 2bjr. (d) CXXC domain of MLL, PDB 2j2s. Colour scheme as for Figure .

Figure 3.

(a) Two CCCH fingers of TIS11d bind an extended stretch of mRNA. Protein colour scheme is as for Figure , RNA is shown in green. PDB: 1rgo. (b) One of the unusual histidine triads from S.pneumoniae PhtA, PDB 2cs7.



Alam SL, Sun J, Payne M et al. (2004) Ubiquitin interactions of NZF zinc fingers. EMBO Journal 23: 1411–1421.

Allen MD, Grummitt CG, Hilcenko C et al. (2006) Solution structure of the nonmethyl‐CpG‐binding CXXC domain of the leukaemia‐associated MLL histone methyltransferase. EMBO Journal 25: 4503–4512.

Beasley SA, Hristova VA and Shaw GS (2007) From the cover: structure of the Parkin in‐between‐ring domain provides insights for E3‐ligase dysfunction in autosomal recessive Parkinson's disease. Proceedings of the National Academy of Sciences of the USA 104: 3095–3100.

Becker PB (2006) Gene regulation: a finger on the mark. Nature 442: 31–32.

Bienz M (2006) The PHD finger, a nuclear protein‐interaction domain. Trends in Biochemical Sciences 31: 35–40.

Deane JE, Ryan DP, Sunde M et al. (2004) Tandem LIM domains provide synergistic binding in the LMO4:Ldb1 complex. EMBO Journal 23: 3589–3598.

Giesecke AV, Fang R, Joung JK (2006) Synthetic protein–protein interaction domains created by shuffling Cys2His2 zinc‐fingers. Molecular Systems Biology 2: 2006.2011.

Grishin NV (2001) Treble clef finger–a functionally diverse zinc‐binding structural motif. Nucleic Acids Research 29: 1703–1714.

Huntley S, Baggott DM, Hamilton AT et al. (2006) A comprehensive catalog of human KRAB‐associated zinc finger genes: insights into the evolutionary history of a large family of transcriptional repressors. Genome Research 16: 669–677.

Liew CK, Simpson RJY, Kwan AHY et al. (2005) Zinc fingers as protein recognition motifs: structural basis for the GATA‐1/Friend of GATA interaction. Proceedings of the National Academy of Sciences of the USA 102: 583–588.

Further Reading

Blindauer CA, Harrison MD, Robinson AK et al. (2002) Multiple bacteria encode metallothioneins and SmtA‐like zinc fingers. Molecular Microbiology 45: 1421–1432.

Blindauer CA and Sadler PJ (2005) How to hide zinc in a small protein. Accounts of Chemical Research 38: 62–69.

DeGuzman RN, Wojciak JM, Martinez‐Yamout MA, Dyson HJ and Wright PE (2005) CBP/p300 TAZ1 domain forms a structured scaffold for ligand binding. Biochemistry 44: 490–497.

Durai S, Mani M, Kandavelou K et al. (2005) Zinc finger nucleases: custom‐designed molecular scissors for genome engineering of plant and mammalian cells. Nucleic Acids Research 33: 5978–5990.

Gamsjaeger R, Liew CK, Loughlin FE, Crossley M and Mackay JP (2007) Sticky fingers: zinc‐fingers as protein‐recognition motifs. Trends in Biochemical Sciences 32: 63–70.

Kelly KF and Daniel JM (2006) POZ for effect – POZ‐ZF transcription factors in cancer and development. Trends in Cell Biology 16: 578–587.

Krishna SS, Majumdar I and Grishin NV (2003) Structural classification of zinc fingers: SURVEY AND SUMMARY. Nucleic Acids Research 31: 532–550.

Papworth M, Kolasinska P and Minczuk M (2006) Designer zinc‐finger proteins and their applications. Gene 366: 27–38.

Ravasi T, Huber T, Zavolan M et al. (2003) Systematic characterization of the zinc‐finger‐containing proteins in the mouse transcriptome. Genome Research 13: 1430–1442.

Schmidt D and Durrett R (2004) Adaptive evolution drives the diversification of zinc‐finger binding domains. Molecular Biology and Evolution 21: 2326–2339.

Web Links

PDB: http://www.pdb.org/

Pfam: http://www.sanger.ac.uk/Software/Pfam/

VEGA: http://vega.sanger.ac.uk/index.html

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How to Cite close
Grant, Richard P, Crossley, M, and Mackay, Joel P(Sep 2007) Zinc‐finger Genes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005047.pub2]