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Supertertiary Structure of the MAGUK Core from PSD-95

Zhang, Jun ; Lewis, Steven M. ; Kuhlman, Brian ; Lee, Andrew L.

Structure, 2013-03, Vol.21 (3), p.402-413 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Supertertiary Structure of the MAGUK Core from PSD-95
Autor: Zhang, Jun ; Lewis, Steven M. ; Kuhlman, Brian ; Lee, Andrew L.
Assuntos: Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; Density ; Disks Large Homolog 4 Protein ; Dynamics ; Escherichia coli - genetics ; Intracellular Signaling Peptides and Proteins - chemistry ; Intracellular Signaling Peptides and Proteins - genetics ; Joining ; Kinases ; Mathematical models ; Membrane Proteins - chemistry ; Membrane Proteins - genetics ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Molecular structure ; Mutation ; Oligopeptides - chemical synthesis ; Oligopeptides - chemistry ; PDZ Domains ; Peptides ; Phosphorylation ; Protein Binding ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Rats ; Recombinant Proteins - chemistry ; Recombinant Proteins - genetics ; Sequence Alignment ; src Homology Domains ; Structure-Activity Relationship ; Synapses
É parte de: Structure, 2013-03, Vol.21 (3), p.402-413
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UNIVERSITYNIH
Descrição: 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. [Display omitted] ► Using NMR and SAXS, we depict the dynamic structure of the MAGUK core PSD-95 ► PDZ3 of the MAGUK core interacts with SH3 via its canonical peptide binding groove ► Binding of PDZ peptides, such as CRIPT, disrupts the interaction between PDZ3 and SH3 ► Rosetta modeling shows that linker residues L411/M412 dock into the PDZ3 binding site Zhang et al. examine the MAGUK core (PDZ3-SH3-GK) of PSD-95 and show how PDZ3 interacts with SH3, with the connecting linker as an adhesive. This dynamic interaction is weakened by PDZ3 ligands and linker phosphorylation, suggesting the central role of domain dynamics in MAGUK function and regulation.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Supertertiary Structure of the MAGUK Core from PSD-95

Zhang, Jun ; Lewis, Steven M. ; Kuhlman, Brian ; Lee, Andrew L.

United States: Elsevier Inc

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