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Figure 4.
Figure 4. The Inhibited Conformation of T β R-I Is
Maintained by the GS Region and the Activation Segment(A) A
ribbon drawing showing the hydrophobic interactions made between
the GS region helices and the top of the kinase β sheet. T β
R-I is viewed from above the kinase N lobe. Thr-204, the site of
a constitutively activating T β R-I mutation ([55]), is
indicated.(B) A ribbon drawing of the complex showing
interactions between the GS loop and the T β R-I kinase, as
well as contacts formed between FKBP12 and T β R-I. Several
interacting residues are shown, with hydrogen bonding indicated
by dashed purple bonds. The L45 loop is indicated.(C) T β R-I
viewed from an oblique angle above the kinase N lobe. The T β
R-II phosphorylation sites are indicated, as are several
residues involved in ionic or polar interactions that stabilize
the placement of the C helix. The movement of the C helix and
the N lobe β sheet into an active conformation appears to be
blocked by the GS loop and a short stretch within the activation
segment. These two steric blockers have been colored magenta.(D)
The same view as in (C), with a molecular surface representation
of the kinase C lobe. The α C side chains have been included to
indicate the space occupied by the helix. The outward rotation
of the C helix and the N lobe β sheet is blocked by the barrier
created by the activation segment.
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