Biomedical Engineering Reference
In-Depth Information
NBD
(a)
IKK
α
Kinase Domain
LZ
HLH
745
NBD
IKK
β
Kinase Domain
LZ
HLH
756
NEMO
CC
CC LZ
ZF
419
(b)
L
Z
L
Z
L
Z
L
Z
H
L
H
H
L
H
H
L
H
H
L
H
K
D
K
D
K
D
P
P
P
P
K
D
VERY LOW
ACTIVITY
HIGH
ACTIVITY
L
Z
L
Z
L
Z
L
Z
K
D
K
D
K
D
P
P
P
P
K
D
LOW
ACTIVITY
INACTIVE
FIGURE 3.1
IKK protein secondary structural motifs and regulation by phosphorylation.
Schematic diagram showing the major known subunits of IKK and their structural and
functional motifs. (a) LZ — leucine zipper; HLH — helix-loop-helix; CC — coiled coil; ZF
— zinc finger; NBD — NEMO binding domain; and amino acid number as indicated at right.
Schematic representation of a model of IKK regulation by phosphorylation. (b) The two
catalytic subunits of IKK are dimerized through their LZ motifs. The HLH motif interacts
with the kinase domain. Phosphorylation of two characterized serines in the activation loop
of IKK initiate kinase activity. The non- or low-phosphorylated C-terminus supports kinase
activation. Active IKK not only phosphorylates its substrates, the IκBs, but also its own C-
terminus by autophosphorylation, thereby inducing a conformational change, which influences
the interaction between HLH motif and kinase domain, resulting in a decrease in kinase
activity. In this state, IKK is more susceptible to further dephosphorylation and inactivation
by phosphatase action.
