9tng

Crystal Structure of the third PDZ domain of PSD-95 protein E401R mutant

spinqualitylabelsall models 9tng, resolution 0.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9tng is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 0.95Å Ligands: ACT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DLG4_HUMAN 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 (By similarity). Publication Abstract from PubMed PSD95, a member of the membrane-associated guanylate kinase family, plays a key role in synaptic transmission. In this multidomain protein, the third PDZ domain has a complex regulatory mechanism that modulates its binding of carboxyl-terminal sequences. Phosphorylation of Tyr397, located in the additional alpha3 helix of this PDZ domain, has been shown to affect the domain's binding affinity. To explore the molecular basis of these changes in affinity, the crystal structure of the mutant Tyr397Glu, a point mutation intended to mimic phosphorylated tyrosine, has been determined. The crystal structure of this mutant reveals conformational changes induced by the introduction of a negative charge into the extra-domain alpha3 helix, suggesting communication between distant secondary-structure elements that may affect the binding affinity of this domain. Additionally, DSC folding studies show a noticeable decrease in the mutant's stability, indicating significant conformational changes. Altogether, the experimental results included in this work demonstrate that alpha3 is part of an electrostatic network that regulates stability and conformational changes at distant sites, including the beta-hairpin at the binding site. Conformational changes on the third PDZ domain of PSD95 upon phosphorylation of Tyr397.,Salinas-Garcia MC, Murciano-Calles J, Andujar-Sanchez M, Ortiz-Salmeron E, Martinez JC, Camara-Artigas A J Struct Biol. 2026 Apr 29;218(2):108322. doi: 10.1016/j.jsb.2026.108322. PMID:42067080 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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