262
N2· ....
•••••••••
H1 hel ices :::--it~!%AI~---lW
N1 ""
H1 helices
N3 ".,
(a)
" '
,.
"
R. E. HARRINGTON et al.
C1
2
....... , .
I
•••• ',IC4
3
H2 helix
4
Fig. 19.3. Tetrameric p53DBD binding to bent B-DNA (a) and to "straight" B-DNA (b). (a) Four
p53DBD subunits bound to bent DNA according to the model (Durell et aI., 1998). The recognition
H2 helices interact with the major groove of DNA (Cho et aI., 1994). The HI-HI interactions are operative in causing DNA bending and twisting (Fig. 19.4). The broken lines indicate that in the wild type
p53 tetramer bound to DNA, the N-termini are located on the external side of the DNA loop, thus
being accessible for interacting with transactivating factors. Whereas, the C-terminal domains are
likely to be on the inside of the loop, facilitating tetramerization of the wild-type p53 protein and
bringing the positively charged basic regions of p53 close to DNA (the tetramerization and basic
domains are not shown). Small arrows denote putative interactions between the proline-rich Nfragments and the p53 core domains (Nagaich et aI., 1999). Large arrows indicate the orientations of
the p53 subunits; they are directed in the same way as the arrows in Fig. 19.2
approximately a 30° to 40° angle. It is also required that the bending occurs into
the major groove of DNA at a tetrad of bases at the pentameric junctions in each
half site, specifically at flexible sequence elements at these positions, i.e., at the
CATG tetrads shown in Fig. 19.2c. This specific DNA bending is required to avoid
two major types of stereochemical clash between the bound p53DBD moieties
(Nagaich et ai., 1997b; Durell et al., 1998). These are illustrated in Fig. 19.3b:
clashes occur between the HI helices of p53DBD peptides bound antiparallel and
N2· ....
•••••••••
H1 hel ices :::--it~!%AI~---lW
N1 ""
H1 helices
N3 ".,
(a)
" '
,.
"
R. E. HARRINGTON et al.
C1
2
....... , .
I
•••• ',IC4
3
H2 helix
4
Fig. 19.3. Tetrameric p53DBD binding to bent B-DNA (a) and to "straight" B-DNA (b). (a) Four
p53DBD subunits bound to bent DNA according to the model (Durell et aI., 1998). The recognition
H2 helices interact with the major groove of DNA (Cho et aI., 1994). The HI-HI interactions are operative in causing DNA bending and twisting (Fig. 19.4). The broken lines indicate that in the wild type
p53 tetramer bound to DNA, the N-termini are located on the external side of the DNA loop, thus
being accessible for interacting with transactivating factors. Whereas, the C-terminal domains are
likely to be on the inside of the loop, facilitating tetramerization of the wild-type p53 protein and
bringing the positively charged basic regions of p53 close to DNA (the tetramerization and basic
domains are not shown). Small arrows denote putative interactions between the proline-rich Nfragments and the p53 core domains (Nagaich et aI., 1999). Large arrows indicate the orientations of
the p53 subunits; they are directed in the same way as the arrows in Fig. 19.2
approximately a 30° to 40° angle. It is also required that the bending occurs into
the major groove of DNA at a tetrad of bases at the pentameric junctions in each
half site, specifically at flexible sequence elements at these positions, i.e., at the
CATG tetrads shown in Fig. 19.2c. This specific DNA bending is required to avoid
two major types of stereochemical clash between the bound p53DBD moieties
(Nagaich et ai., 1997b; Durell et al., 1998). These are illustrated in Fig. 19.3b:
clashes occur between the HI helices of p53DBD peptides bound antiparallel and