期刊
STRUCTURE
卷 19, 期 11, 页码 1711-1722出版社
CELL PRESS
DOI: 10.1016/j.str.2011.07.018
关键词
-
资金
- National Institutes of Health [AI508072]
Here, we report a novel mechanism of PDZ (PSD-95/DIg/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.
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