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Figure 5.
Figure 5. Rearrangement of Helix αC
(A) Superimposition
of central residues in the PAK5 αC helices showing the
remodeling of the αC termini. The central residues stay in
position, whereas conversion into an active state (PAK5 purine
complex) results in the addition of an N-terminal α helix and
disruption of the αC terminus.
(B) Structural changes at
the αC C terminus brings Asn493 (Asn365, PAK4) into position to
hydrogen bond with the DFG glycine (Gly588) and a conserved
activation segment cysteine (Cys590 and Cys462 in PAK5 and PAK4,
respectively), resulting in the formation of the αC anchor
point with the activation segment. In the PAK4 structures, this
movement is not completed, and only one hydrogen bond is formed
with Cys462.
(C) Swinging movement of the conserved αC
Arg487 (Arg359 in PAK4) between the glycine-rich loop and the
phosphoserine activation loop residue. Upon extension of the αC
helix by one turn at the N –terminus, Arg487 forms three
hydrogen bonds with the glycine-rich loop, stabilizing an
extremely closed conformation (PAK5 purine complex, orange). In
the short αC conformation, the corresponding arginine in PAK4
interacts with the phosphoserine residue in the activation
segment. This conformation also results in a partially open
conformation of the glycine-rich loop stabilized by a hydrogen
bond formed by the conserved Gln357. When αC swings away (as
observed in apo-PAK5, cyan, or PAK6 [not shown]), the N- and
C-terminal anchor points break, resulting in an open
glycine-rich loop conformation. During the swinging movement,
Arg487 in the PAK5 apo structure was observed in a disordered
state beyond the γ carbon (indicated by white balls and
sticks).
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