1RZX

Crystal Structure of a Par-6 PDZ-peptide Complex

Summary for 1RZX

• Entry DOI: 10.2210/pdb1rzx/pdb
• Descriptor: CG5884-PA, Acetylated VKESLV Peptide (3 entities in total)
• Functional Keywords: cell cycle
• Biological source: Drosophila melanogaster (fruit fly); More
• Total number of polymer chains: 2
• Total formula weight: 11197.85

Authors

Peterson, F.C.,Penkert, R.R.,Volkman, F.B.,Prehoda, K.E. (deposition date: 2003-12-29, release date: 2004-01-27, Last modification date: 2024-10-30)

Primary citation

Peterson, F.C.,Penkert, R.R.,Volkman, B.F.,Prehoda, K.E.
Cdc42 regulates the Par-6 PDZ domain through an allosteric CRIB-PDZ transition.
Mol.Cell, 13:665-676, 2004

PubMed Abstract: Regulation of protein interaction domains is required for cellular signaling dynamics. Here, we show that the PDZ protein interaction domain from the cell polarity protein Par-6 is regulated by the Rho GTPase Cdc42. Cdc42 binds to a CRIB domain adjacent to the PDZ domain, increasing the affinity of the Par-6 PDZ for its carboxy-terminal ligand by approximately 13-fold. Par-6 PDZ regulation is required for function as mutational disruption of Cdc42-Par-6 PDZ coupling leads to inactivation of Par-6 in polarized MDCK epithelial cells. Structural analysis reveals that the free PDZ domain has several deviations from the canonical PDZ conformation that account for its low ligand affinity. Regulation results from a Cdc42-induced conformational transition in the CRIB-PDZ module that causes the PDZ to assume a canonical, high-affinity PDZ conformation. The coupled CRIB and PDZ architecture of Par-6 reveals how simple binding domains can be combined to yield complex regulation.

PubMed: 15023337
DOI: 10.1016/S1097-2765(04)00086-3

Experimental method

X-RAY DIFFRACTION (2.1 Å)