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Figure 6.
Figure 6. Par-6 PDZ Peptide Binding Induces Conversion to
the High-Affinity Conformation(A) The free Par-6 PDZ domain
exists in a low-affinity conformation (green) that deviates from
the canonical PDZ conformation. Binding of Cdc42 or peptide
induces conversion to the high-affinity form (orange). Once one
ligand has bound, the other ligand binds with an enhanced
affinity (by a cooperativity factor, c).(B) The Drosophila Par-6
PDZ-VKESLV peptide complex structure. Electron density for the
peptide from a 2F[o] − F[c] map in which the peptide was
omitted from the calculation of the phases is shown.(C)
Comparison of the crystal structure of Par-6 in complex with
VKESLV peptide (orange) and Cdc42-bound Par-6 and PSD-95 PDZ3
(both black).(D) Structure of the peptide binding pocket. The
Par-6 PDZ domain (orange) is shown with bound peptide
(violet).(E) Spatial and temporal Par-6 regulation model. Cdc42
is lipid modified and becomes associated with the membrane when
activated, which may play a role in Par-6 localization thereby
coupling membrane translocation with activity modulation.
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