A conformational switch in the CRIB-PDZ module of Par-6.
Structure
; 19(11): 1711-22, 2011 Nov 09.
Article
em En
| MEDLINE
| ID: mdl-22078569
ABSTRACT
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 CRIBPDZ 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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteína Quinase C
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Proteínas de Drosophila
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Domínios PDZ
Limite:
Animals
Idioma:
En
Revista:
Structure
Assunto da revista:
BIOLOGIA MOLECULAR
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BIOQUIMICA
/
BIOTECNOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos