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http://purl.uniprot.org/citations/34538002http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/34538002http://www.w3.org/2000/01/rdf-schema#comment"Chemical synaptic transmission represents the most sophisticated dynamic process and is highly regulated with optimized neurotransmitter balance. Imbalanced transmitters can lead to transmission impairments, for example, intracellular zinc accumulation is a hallmark of degenerating neurons. However, the underlying mechanisms remain elusive. Postsynaptic density protein-95 (PSD-95) is a primary postsynaptic membrane-associated protein and the major scaffolding component in the excitatory postsynaptic densities, which performs substantial functions in synaptic development and maturation. Its membrane association induced by palmitoylation contributes largely to its regulatory functions at postsynaptic sites. Unlike other structural domains in PSD-95, the N-terminal region (PSD-95NT) is flexible and interacts with various targets, which modulates its palmitoylation of two cysteines (C3/C5) and glutamate receptor distributions in postsynaptic densities. PSD-95NT contains a putative zinc-binding motif (C2H2) with undiscovered functions. This study is the first effort to investigate the interaction between Zn2+ and PSD-95NT. The NMR titration of 15 N-labeled PSD-95NT by ZnCl2 was performed and demonstrated Zn2+ binds to PSD-95NT with a binding affinity (Kd ) in the micromolar range. The zinc binding was confirmed by fluorescence and mutagenesis assays, indicating two cysteines and two histidines (H24, H28) are critical residues for the binding. These results suggested the concentration-dependent zinc binding is likely to influence PSD-95 palmitoylation since the binding site overlaps the palmitoylation sites, which was verified by the mimic PSD-95 palmitoyl modification and intact cell palmitoylation assays. This study reveals zinc as a novel modulator for PSD-95 postsynaptic membrane association by chelating its N-terminal region, indicative of its importance in postsynaptic signaling."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.org/dc/terms/identifier"doi:10.1002/pro.4187"xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/author"Gonzalez A."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/author"Li L."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/author"Hell J.W."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/author"Zhang Y."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/author"Fang X."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/author"Vega A."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/author"Salinas A."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/author"Ames J.B."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/author"Guerra L."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/author"Garza C."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/author"Tsin A."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/author"Ascota L."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/name"Protein Sci"xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/pages"2246-2257"xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/title"Zinc-chelating postsynaptic density-95 N-terminus impairs its palmitoyl modification."xsd:string
http://purl.uniprot.org/citations/34538002http://purl.uniprot.org/core/volume"30"xsd:string
http://purl.uniprot.org/citations/34538002http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/34538002
http://purl.uniprot.org/citations/34538002http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/34538002
http://purl.uniprot.org/uniprot/#_B7Z3U2-mappedCitation-34538002http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34538002
http://purl.uniprot.org/uniprot/#_B7Z4H2-mappedCitation-34538002http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34538002
http://purl.uniprot.org/uniprot/#_B7Z647-mappedCitation-34538002http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34538002