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From Proteopedia
NMR Derived Structure of Ca2+ Calmodulin bound to Phosphorylated PSD-95
Structural highlights
Function[CALM_XENLA] Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. [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 PubMedPostsynaptic density protein-95 (PSD-95) localizes AMPA-type glutamate receptors (AMPARs) to postsynaptic sites of glutamatergic synapses. Its postsynaptic displacement is necessary for loss of AMPARs during homeostatic scaling down of synapses. Here, we demonstrate that upon Ca(2+) influx, Ca(2+)/calmodulin (Ca(2+)/CaM) binding to the N-terminus of PSD-95 mediates postsynaptic loss of PSD-95 and AMPARs during homeostatic scaling down. Our NMR structural analysis identified E17 within the PSD-95 N-terminus as important for binding to Ca(2+)/CaM by interacting with R126 on CaM. Mutating E17 to R prevented homeostatic scaling down in primary hippocampal neurons, which is rescued via charge inversion by ectopic expression of CaM(R)(126E), as determined by analysis of miniature excitatory postsynaptic currents. Accordingly, increased binding of Ca(2+)/CaM to PSD-95 induced by a chronic increase in Ca(2+) influx is a critical molecular event in homeostatic downscaling of glutamatergic synaptic transmission. Ca(2+)/calmodulin binding to PSD-95 mediates homeostatic synaptic scaling down.,Chowdhury D, Turner M, Patriarchi T, Hergarden AC, Anderson D, Zhang Y, Sun J, Chen CY, Ames JB, Hell JW EMBO J. 2018 Jan 4;37(1):122-138. doi: 10.15252/embj.201695829. Epub 2017 Nov 8. PMID:29118000[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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