title: Supertertiary structure of the MAGUK core from PSD-95.
abstract: The family of membrane-associated guanylate kinase (MAGUK) scaffold proteins comprises members that function at neuronal synapses, tight junctions, immunological synapses, and neutrophil membranes. Through their multiple domains, MAGUKs organize events of signal transduction, cell adhesion, and molecular trafficking. Here, we use nuclear magnetic resonance, small-angle X-ray scattering, and Rosetta modeling to reveal the structural preferences and interdomain dynamics of the MAGUK core (PDZ3-SH3-guanylate kinase) from postsynaptic density-95 (PSD-95), the best known MAUGK. PSD-95 is highly abundant in the postsynaptic density of excitatory neurons and is responsible for coupling glutamate receptors with internal postsynaptic structures. These solution-based studies show that the MAGUK core PDZ domain (PDZ3) interacts directly with the SH3 domain via its canonical peptide binding groove, with the connecting linker serving as an adhesive. This weak interaction, however, is dynamic and weakened further by PDZ3 ligands and linker phosphorylation, suggesting that domain dynamics may be central to MAGUK function.
authors: Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, NC 27599-7568, USA.
authors: Jun
authors: J
authors: Zhang
authors: Steven M
authors: SM
authors: Lewis
authors: Brian
authors: B
authors: Kuhlman
authors: Andrew L
authors: AL
authors: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D000076122:Disks Large Homolog 4 Protein; D004926:Escherichia coli / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009154:Mutation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D054731:PDZ Domains; D010766:Phosphorylation; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D018909:src Homology Domains
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009842:Oligopeptides; D011994:Recombinant Proteins