2mes

Backbone 1H, 13C, 15N resonance assignments of calcium-bound calmodulin in complex with PSD95 N-terminal peptide

spinqualitylabelsall models 2mes Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2mes is a 2 chain structure with sequence from Homo sapiens and Xenopus laevis. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: CA 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 Postsynaptic density protein-95 (PSD-95) is a central element of the postsynaptic architecture of glutamatergic synapses. PSD-95 mediates postsynaptic localization of AMPA receptors and NMDA receptors and plays an important role in synaptic plasticity. PSD-95 is released from postsynaptic membranes in response to Ca(2+) influx via NMDA receptors. Here, we show that Ca(2+)/calmodulin (CaM) binds at the N-terminus of PSD-95. Our NMR structure reveals that both lobes of CaM collapse onto a helical structure of PSD-95 formed at its N-terminus (residues 1-16). This N-terminal capping of PSD-95 by CaM blocks palmitoylation of C3 and C5, which is required for postsynaptic PSD-95 targeting and the binding of CDKL5, a kinase important for synapse stability. CaM forms extensive hydrophobic contacts with Y12 of PSD-95. The PSD-95 mutant Y12E strongly impairs binding to CaM and Ca(2+)-induced release of PSD-95 from the postsynaptic membrane in dendritic spines. Our data indicate that CaM binding to PSD-95 serves to block palmitoylation of PSD-95, which in turn promotes Ca(2+)-induced dissociation of PSD-95 from the postsynaptic membrane. Capping of the N-terminus of PSD-95 by calmodulin triggers its postsynaptic release.,Zhang Y, Matt L, Patriarchi T, Malik ZA, Chowdhury D, Park DK, Renieri A, Ames JB, Hell JW EMBO J. 2014 Jun 17;33(12):1341-53. doi: 10.1002/embj.201488126. Epub 2014 Apr 4. PMID:24705785 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Calmodulin 3D structures

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