Structural characterization of the intramolecular interaction between the SH3 and guanylate kinase domains of PSD-95.
PSD-95/SAP90 is a member of the MAGUK superfamily. In excitatory synapses, PSD-95 clusters receptors and ion channels at specific sites in the postsynaptic membrane and organizes downstream signaling and cytoskeletal molecules. We have determined the crystal structures of the apo and GMP-bound forms to 2.3 and 2.0 A resolutions, respectively, of a fragment containing the SH3, HOOK, and guanylate kinase (GK) domains of PSD-95. We observe an intramolecular interaction between the SH3 and GK domains involving the formation of a beta sheet including residues N- and C-terminal to the GK domain. Based on amino acid conservation and mutational data available in the literature, we propose that this intramolecular interaction is a common feature among MAGUK proteins.
Tavares
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GA
The Howard Hughes Medical Institute and Department of Molecular and Cellular Physiology, Stanford University, 1201 Welch Road P210 MSLS, Stanford, CA 94305, USA.
Panepucci
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EH
Brunger
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AT
D000595:Amino Acid Sequence; D000818:Animals; D001051:Apoenzymes / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D000076122:Disks Large Homolog 4 Protein; D006157:Guanosine Monophosphate / Q000378:metabolism; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D016415:Sequence Alignment; D055672:Static Electricity; D013329:Structure-Activity Relationship; D018909:src Homology Domains
D001051:Apoenzymes; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C501451:Mpp2 protein, rat; D009419:Nerve Tissue Proteins; C033652:postsynaptic density proteins; D006157:Guanosine Monophosphate; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases