Chemistry Reference
In-Depth Information
Fig. 2 (a) Ribbon diagram of the Gfizf35-DNA complex (PDB: 2kmk) with the zinc ions shown
as
gray spheres
and the side-chains of two coordinated histidines and two cysteines shown in sticks
and DNA shown in
yellow sticks
.(b) Solution structure of the RNA complex of TIS11d (PDB:
1rgo) with the zinc ions in
gray spheres
coordinated to three cysteines and one histidine and RNA
shown as
yellow sticks
.(c) Solution structure of HypA from
Helicobacter pylori
(PDB: 2kdx) with
the zinc ions in
gray sphere
coordinated to four cysteine sulfurs
transcriptional activation, regulation of apoptosis, protein folding and assembly, as
well as lipid binding [
52
,
56
,
57
]. Comprehensive reviews in this area can be found
[
56
-
58
]. Here, we will only highlight some of the recent studies. Solution structure
of Gfi-1 zinc finger 3-5 complex with a 16-mer consensus DNA (Fig.
2a
)
demonstrated that zinc fingers 3-5 bind into the major groove of the target DNA,
reminiscent of canonical Cys
2
His
2
zinc-finger domains, which provide valuable
insight into the structure determinants for DNA binding specificity as well as
molecular rationales for a naturally occurring mutation that causes acute myeloid
leukemia [
59
]. Poly(ADP-ribose) (PAR) is an important post-translational modifi-
cation in higher eukaryotes. Solution structures of two PBZ modules (PAR-binding
zinc finger) of PNK-like factor (APLF) and the PDB domain of
Drosophila
melanogaster
CG1218-PA reveal a novel type of Cys
2
His
2
zinc finger and provide
a structural basis for PBZ-PAR recognition. Intriguingly, Cys
2
His
2
zinc coordina-
tion of the PBZ modules is structurally and functionally dissimilar from canonical
double stranded DNA-binding TFIIIA-type zinc fingers; rather they resemble
single-stranded RNA-binding Cys
3
His
1
tandem zinc fingers (TZFs). Both of them
lack secondary structures but have rigid backbone conformations as a result of zinc
binding [
60
,
61
]. Zinc finger proteins are also able to bind to RNA. The NMR
structure of tandem zinc finger (TZF) domain of the protein TIS11d bound to the
RNA sequence 5
0
-UUAUUUAUU-3
0
(Fig.
2b
) reveals a pair of novel Cys
3
His
1
fingers which independently recognizes the four nucleotide sequence UAUU and
the sequence specificity in RNA recognition is achieved by a network of intermo-
lecular hydrogen bonds [
62
]. This structure provides insights into RNA-binding
function of this family of Cys
3
His
1
zinc finger proteins [
62
]. The Cys
3
His
1
zinc
finger motif is also found in the structure of SAP30 polypeptide of the Sin3
corepressor complex which adopts a novel fold comprising two
b
-strands and two
a
-helices with the zinc organized center. Such a structure may also function as
a double-stranded DNA-binding motif [
63
]. The zinc finger CW (zf-CW) domain