Penkert Rhiannon R, DiVittorio Heather M, Prehoda Kenneth E
Institute of Molecular Biology and Department of Chemistry, University of Oregon, Eugene, Oregon 97403, USA.
Nat Struct Mol Biol. 2004 Nov;11(11):1122-7. doi: 10.1038/nsmb839. Epub 2004 Oct 10.
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.
PDZ蛋白相互作用结构域通常对C端配体具有选择性，但也已鉴定出非C端的“内部”配体。细胞极性蛋白Par-6的PDZ结构域结合C端配体以及来自Pals1/星尘蛋白的内部序列。Pals1-Par-6 PDZ复合物的结构表明，PDZ配体结合位点发生变形以允许内部结合。虽然Rho GTP酶Cdc42与Par-6 PDZ相邻的CRIB结构域结合可调节C端配体的结合，但Pals1结合时发生的构象变化使其结合独立于Cdc42。这些结果提示了一种机制，通过该机制PDZ配体可以很容易地绕过对C端的需求，并揭示了Par-6中一组复杂的协同和竞争相互作用，这些相互作用可能对细胞极性调节很重要。
