2ka9 | pdb_00002ka9

Solution structure of PSD-95 PDZ12 complexed with cypin peptide

spinqualitylabelsall models 2ka9, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ka9 is a 3 chain structure with sequence from Buffalo rat. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: Dlg4, Dlgh4, Psd95 (Buffalo rat) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DLG4_RAT] Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The two N-terminal PDZ domains of postsynaptic density protein-95 (PDS-95 PDZ1 and PDZ2) are closely connected in tandem by a conserved peptide linker of five amino acids. The interdomain orientation between PDZ1 and PDZ2 of the ligand-free PDZ12 tandem is restrained, and this conformational arrangement facilitates the synergistic binding of PDZ12 to multimeric targets. (1) The interdomain orientation of the target-bound state of PDZ12 is not known. Here, we have solved the structure of PDZ12 in complex with its binding domain from cypin. Both chemical shift data and residual dipolar coupling measurements showed that the restrained interdomain orientation disappeared upon cypin peptide binding. NMR-based relaxation experiments revealed slow interdomain motions in the PDZ12/cypin peptide complex. Molecular dynamics simulations also showed that the PDZ12/cypin complex has larger conformational flexibility than the ligand-free PDZ12. This dramatic change of protein dynamics provides extra conformational entropy upon ligand binding, thus enhancing the ligand binding affinity of the PDZ12 tandem. Modulation of ligand binding affinity through concerted interdomain structural and dynamic rearrangements may represent a general property of multidomain scaffold proteins. Creating conformational entropy by increasing interdomain mobility in ligand binding regulation: a revisit to N-terminal tandem PDZ domains of PSD-95.,Wang W, Weng J, Zhang X, Liu M, Zhang M J Am Chem Soc. 2009 Jan 21;131(2):787-96. PMID:19072119 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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