Biomedical Engineering Reference
In-Depth Information
has been shown to bind to a large and diverse array of disordered partners that
fold upon binding to KIX. The phosphorylated kinase interaction domain of
CREB (pKID) is disordered in the free state
34
and folds upon binding to KIX.
5
Phosphorylation does not affect the conformational equilibrium in free KID,
34
indicating that the increased affinity of the phosphorylated form is not due to
the formation of a pre-equilibrium containing folded forms, but rather to
enthalpy terms related to the charge of the phosphorylated Ser 133 of CREB.
35
Somewhat surprisingly, KIX binds disordered partners in at least two surface
sites (Figure 5.2), which promotes a small allosteric effect when two partners
are bound.
36,37
Figure 5.2
(A) Superposition of a ternary complex of the KIX domain of CBP with
c-Myb, a constitutive transcriptional activator regulating hematopoietic
cell growth and differentiation and the mixed lineage leukemia protein
MLL
37
(KIX: light blue, c-Myb: red, MLL: green) with the KIX:c-Myb
binary complex
88
(KIX: yellow, c-Myb: pink), showing the movement of
loop L
12
and helix G
2
and the elongation of KIX helix a
3
in the ternary
complex (shown in darker blue). (B) Close-up view of the same
superposition as in (a), showing E665 and E666, which are in the
disordered region of KIX in the c-Myb complex, moved into closer
proximity to the c-Myb residues K291 and R294 upon folding of the C-
terminal end of KIX helix a
3
in the ternary complex. Adapted from ref.
37 with permission. # Elsevier, 2006.
