2.4.1 Descriptive Examples,
One of the fi rst three - dimensional structures of a zinc - fi nger domain, deter-
mined by nuclear magnetic resonance (NMR) spectroscopy, was published in
Science magazine in 1989.^35 The structure showed what is now known as a
typical, compact zinc - fi nger domain with the tertiary structure featuring two
antiparallelβ - sheets and one α - helical region — the ββα motif. The structure
visualizes a synthetic construct corresponding to the 31st zinc - fi nger motif
from theXenopus (frog) oocyte protein (Xfi n - 31). Figure 2.21 is a visualization
of the Xfi n - 31 zinc - fi nger domain rendered from data deposited in the protein
data bank (PDB: 1ZNF, found at website http://www.rcsb.org/pdb ). The zinc
ion, buried in the interior of the protein, is shown in silver space fi ll form, with
its cys and his ligands in stick format. The ligands cys3 (in β - sheet 1) and cys6
(in the loop connecting the two antiparallelβ - sheets) are shown above and in
front of the Zn ion conforming to the zinc - fi nger pattern CX 2 C. The cysteines
ligate to the zinc ion through their S γ atoms (shown as dark gray). The ligands
his19 and his23, having their N ε atoms as zinc ion ligands (histidine nitrogens
shown in black), are positioned in the α - helical region below and to the right
of the zinc ion in Figure 2.21 , conforming to the zinc - fi nger pattern HX 3 H.
Residues 1 – 10 of the construct form an antiparallel β - sheet domain with the
β - sheets connected by a tight turn. A short loop leads to the α - helical domain,
comprised of residues 12 – 24. Hydrogen bonds conforming to those typical for
antiparallelβ - sheets: (1) tyr1 N – H · · · O – C phe10 and (2) phe10 N – H · · · O – C tyr1.
The α - helical N – H · · · O – C hydrogen bonds form between the residues: 16 → 12,
17 → 13, 18 → 14, 19 → 15, and 20 → 16. The helical motif then changes to a 3 10
pattern with N – H · · · O – C hydrogen bonds form between the residues: 21 → 18,
22 → 19, and 23 → 20. This early zinc - fi nger protein NMR solution structure has
been followed by a great variety of both X - ray crystallographic and NMR
solution studies — in late 2006, a search of the protein data bank (PDB) for
“ zincfi nger protein ” yielded 994 hits. Several of these will be discussed
below.
The X - ray crystallographic structure from the mouse protein Zif268 and a
consensus DNA - binding site has been determined at 2.1 - Å resolution, as
reported by the authors of reference 31 (deposited as PDB: 1ZAA; see Figure
2.22 ). In this complex, the zinc fi ngers bind in the major groove of B - DNA
and wrap part way around the double helix. Each zinc - fi nger domain consists
of two antiparallelβ - sheets containing two cys ligands (one cysteine in the
loop connecting the two antiparallelβ - sheets) and an α - helix containing two
histidine ligands. In Figure 2.22 , the polypeptide chain is shown in cartoon
form: The Zn(II) ions are shown in sphere format, while the histidines and the
cysteines ligands are shown in stick format. The DNA double - helix segment
is shown in ribbon form with two interacting guanines (G4 and G7) shown in
stick format. The interatomic distance between Zn(1) and Zn(2) is 26.6 Å , and
the interatomic distance between Zn(2) and Zn(3) is 27.4 Å. Each fi nger has
a similar relation to the DNA and makes its primary contacts in a three - base
ZINC-FINGER PROTEINS 67
