Abstract
Membrane-associated guanylate kinases (MAGUKs), such as PSD-95, are modular scaffolds that organize signaling complexes at synapses and other cell junctions. MAGUKs contain PDZ domains, which recruit signaling proteins, as well as a Src homology 3 (SH3) and a guanylate kinase-like (GK) domain, implicated in scaffold oligomerization. The crystal structure of the SH3-GK module from PSD-95 reveals that these domains form an integrated unit: the SH3 fold comprises noncontiguous sequence elements divided by a hinge region and the GK domain. These elements compose two subdomains that can assemble in either an intra- or intermolecular fashion to complete the SH3 fold. We propose a model for MAGUK oligomerization in which complementary SH3 subdomains associate by 3D domain swapping. This model provides a possible mechanism for ligand regulation of oligomerization.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Apoenzymes / chemistry
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Apoenzymes / metabolism
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Binding Sites
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Catalytic Domain*
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Crystallography, X-Ray
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Disks Large Homolog 4 Protein
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Guanine / metabolism
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Guanylate Kinases
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Intracellular Signaling Peptides and Proteins
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Ligands
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Membrane Proteins
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Models, Biological
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Models, Molecular
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry*
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Nerve Tissue Proteins / metabolism*
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Nucleoside-Phosphate Kinase / chemistry*
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Nucleoside-Phosphate Kinase / metabolism*
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Protein Binding
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Rats
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Sequence Alignment
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src Homology Domains*
Substances
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Apoenzymes
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Intracellular Signaling Peptides and Proteins
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Ligands
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Membrane Proteins
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Mpp2 protein, rat
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Nerve Tissue Proteins
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postsynaptic density proteins
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Guanine
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Nucleoside-Phosphate Kinase
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Guanylate Kinases