Figure 3.
Figure 3. Peptide recognition by WDR5 and conformational changes
upon peptide binding. (a) The peptide is recognized by an
elaborate series of direct and indirect contacts. Orientation of
the peptide–WDR5 complex is the same as in the lower panel of
Figure 1c. The majority of direct contacts from WDR5 are made to
the N terminus and the first three residues. These residues
adopt an approximately helical main chain conformation, with one
hydrogen bond between the A1 and K4 backbone. Water-mediated
contacts are important in recognition of the C-terminal residues
of the peptide, as all waters shown (red spheres) are conserved
among the peptide-bound structures. Tyr191 apparently acts as a
central platform in this peptide-bound water network. (b) Phe133
and Phe263 form an aromatic sandwich about the R2 guanidinium
moiety, equatorially flanked by a number of backbone
carbonyl–mediated hydrogen bonds. These tight hydrogen bonds
are thought to impart specificity for arginine over
dimethyllysine, particularly the one from N of
R2 to the Ser91 carbonyl. (c) Apparent coordinated movement of
Phe133 and Phe149 to form the top of the aromatic sandwich
recognition element when peptide is bound. The relevant
apostructure side chains are depicted in gray and a
representative liganded structure (H3K4me2 complex I) is in
crimson. (d) Retraction of the loop bearing Lys259 causes a
reorganization of the residues lining the central cavity, which
permits tight R2 coordination. Coloring is as in c. This
movement may be driven by a steric clash between this lysine and
the incoming peptide Q5 side chain.
The above figure is reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2006,
13,
704-712)
copyright 2006.
of
R2 to the Ser91 carbonyl. (c) Apparent coordinated movement of
Phe133 and Phe149 to form the top of the aromatic sandwich
recognition element when peptide is bound. The relevant
apostructure side chains are depicted in gray and a
representative liganded structure (H3K4me2 complex I) is in
crimson. (d) Retraction of the loop bearing Lys259 causes a
reorganization of the residues lining the central cavity, which
permits tight R2 coordination. Coloring is as in c. This
movement may be driven by a steric clash between this lysine and
the incoming peptide Q5 side chain.