Biomedical Engineering Reference
In-Depth Information
(A)
1
H-
15
N HSQC spectra of the intrinsically disordered transactivation
domain of STAT2 free (black) and bound to TAZ1 (red).
52
(B) One
member of an ensemble of structures of the complex formed by the CBP
TAZ1 domain (blue) and STAT2-TAD (pink).
52
Figure 5.6
unstable, and is apparently degraded in a ubiquitin-independent manner by the
20S proteasome.
56
Removal of IkBa from NFkB frees the nuclear localisation
signal on the RelA domain of NFkB, mediating translocation to the nucleus,
where binding to the kB DNA sequence and transcription of genes can occur.
Interestingly, genes transcribed as a consequence of NFkB activation
frequently include that for IkBa, which is thus re-synthesised and employed
to remove NFkB from the DNA to turn off the signal. The re-formed NFkB-
IkBa complex returns to the cytoplasm to await the next signal. Most of the
binding energy for this complex is due to coupled folding and binding
interactions at either end of the IkBa ankyrin repeat domain.
57
The C-terminal
region of IkBa (ankyrin repeats 5 and 6 and the PEST-containing sequence)
folds from a loose molten globule-like state in the free protein into a stable
cooperatively folded state upon binding to NFkB.
58,59
At the other end of the
molecule,
the
disordered
partner
is
part
of
NFkB:
the
RelA
nuclear
