Internal recognition through PDZ domain plasticity in the Par-6-Pals1 complex.
PDZ protein interaction domains are typically selective for C-terminal ligands, but non-C-terminal, 'internal' ligands have also been identified. The PDZ domain from the cell polarity protein Par-6 binds C-terminal ligands and an internal sequence from the protein Pals1/Stardust. The structure of the Pals1-Par-6 PDZ complex reveals that the PDZ ligand-binding site is deformed to allow for internal binding. Whereas binding of the Rho GTPase Cdc42 to a CRIB domain adjacent to the Par-6 PDZ regulates binding of C-terminal ligands, the conformational change that occurs upon binding of Pals1 renders its binding independent of Cdc42. These results suggest a mechanism by which the requirement for a C terminus can be readily bypassed by PDZ ligands and reveal a complex set of cooperative and competitive interactions in Par-6 that are likely to be important for cell polarity regulation.
Institute of Molecular Biology and Department of Chemistry, University of Oregon, Eugene, Oregon 97403, USA.
Rhiannon R
RR
Penkert
Heather M
HM
DiVittorio
Kenneth E
KE
Prehoda
D000595:Amino Acid Sequence; D000818:Animals; D016880:Anisotropy; D001667:Binding, Competitive; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry / Q000502:physiology*; D004331:Drosophila melanogaster; D005982:Glutathione Transferase / Q000378:metabolism; D051528:Guanylate Kinases; D008024:Ligands; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000502:physiology*; D008954:Models, Biological; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
D029721:Drosophila Proteins; D008024:Ligands; D026901:Membrane Transport Proteins; D011506:Proteins; D005982:Glutathione Transferase; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; C444479:sdt protein, Drosophila; D020764:cdc42 GTP-Binding Protein