'Zinc finger' domains
[1][2][3][5] are nucleic acid-binding protein structures first
identified in the Xenopus transcription factor TFIIIA. These domains have
since been found in numerous nucleic acid-binding proteins. A zinc finger
domain is composed of 25 to 30 amino-acid residues. There are two cysteine or
histidine residues at both extremities of the domain, which are involved in
the tetrahedral coordination of a zinc atom. It has been proposed that such a
domain interacts with about five nucleotides. A schematic representation of a
zinc finger domain is shown below:
x x
x x
x x
x x
x x
x x
C H
x \ / x
x Zn x
x / \ x
C H
x x x x x x x x x x
Many classes of zinc fingers are characterized according to the number and
positions of the histidine and cysteine residues involved in the zinc atom
coordination. In the first class to be characterized, called C2H2, the first
pair of zinc coordinating residues are cysteines, while the second pair are
histidines. A number of experimental reports have demonstrated the zinc-
dependent DNA or RNA binding property of some members of this class.
Some of the proteins known to include C2H2-type zinc fingers are listed below.
We have indicated, between brackets, the number of zinc finger regions found
in each of these proteins; a '+' symbol indicates that only partial sequence
data is available and that additional finger domains may be present.
- Saccharomyces cerevisiae: ACE2 (3), ADR1 (2), AZF1 (4), FZF1 (5), MIG1 (2),
MSN2 (2), MSN4 (2), RGM1 (2), RIM1 (3), RME1 (3), SFP1 (2), SSL1 (1),
STP1 (3), SWI5 (3), VAC1 (1) and ZMS1 (2).
- Emericella nidulans: brlA (2), creA (2).
- Drosophila: AEF-1 (4), Cf2 (7), ci-D (5), Disconnected (2), Escargot (5),
Glass (5), Hunchback (6), Kruppel (5), Kruppel-H (4+), Odd-skipped (4),
Odd-paired (4), Pep (3), Snail (5), Spalt-major (7), Serependity locus beta
(6), delta (7), h-1 (8), Suppressor of hairy wing su(Hw) (12), Suppressor
of variegation suvar(3)7 (5), Teashirt (3) and Tramtrack (2).
- Xenopus: transcription factor TFIIIA (9), p43 from RNP particle (9), Xfin
(37 !!), Xsna (5), gastrula XlcGF5.1 to XlcGF71.1 (from 4+ to 11+), Oocyte
XlcOF2 to XlcOF22 (from 7 to 12).
- Mammalian: basonuclin (6), BCL-6/LAZ-3 (6), erythroid krueppel-like
transcription factor (3), transcription factors Sp1 (3), Sp2 (3), Sp3 (3)
and Sp(4) 3, transcriptional repressor YY1 (4), Wilms' tumor protein (4),
EGR1/Krox24 (3), EGR2/Krox20 (3), EGR3/Pilot (3), EGR4/AT133 (4), Evi-1
(10), GLI1 (5), GLI2 (4+), GLI3 (3+), HIV-EP1/ZNF40 (4), HIV-EP2 (2), KR1
(9+), KR2 (9), KR3 (15+), KR4 (14+), KR5 (11+), HF.12 (6+), REX-1 (4), ZfX
(13), ZfY (13), Zfp-35 (18), ZNF7 (15), ZNF8 (7), ZNF35 (10), ZNF42/MZF-1
(13), ZNF43 (22), ZNF46/Kup (2), ZNF76 (7), ZNF91 (36), ZNF133 (3).
In addition to the conserved zinc ligand residues it has been shown
[4] that a
number of other positions are also important for the structural integrity of
the C2H2 zinc fingers. The best conserved position is found four residues
after the second cysteine; it is generally an aromatic or aliphatic residue. A
profile was also developed that spans the whole domain.