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Publication : A conformational switch in the CRIB-PDZ module of Par-6.

First Author  Whitney Dustin S Year  2011
Journal  Structure Volume  19
Pages  1711-22 PubMed ID  22078569
Abstract Text  Here, we report a novel mechanism of PDZ (PSD-95/Dlg/ZO-1) domain regulation that distorts a conserved element of PDZ ligand recognition. The polarity regulator Par-6 assembles a conserved multiprotein complex and is directly modulated by the Rho GTPase Cdc42. Cdc42 binds the adjacent Cdc42/Rac interactive binding (CRIB) and PDZ domains of Par-6, increasing C-terminal ligand binding affinity by 10-fold. By solving structures of the isolated PDZ domain and a disulfide-stabilized CRIB-PDZ, we detected a conformational switch that controls affinity by altering the configuration of the conserved "GLGF"loop. As a result, lysine 165 is displaced from the PDZ core by an adjacent hydrophobic residue, disrupting coordination of the PDZ ligand-binding cleft. Stabilization of the CRIB:PDZ interface restores K165 to its canonical location in the binding pocket. We conclude that a unique "dipeptide switch"in the Par-6 PDZ transmits a signal for allosteric activation to the ligand-binding pocket. Doi  10.1016/j.str.2011.07.018
Issue  11 Month  Nov

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