Abstract
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.
Publication types
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Apoenzymes / chemistry
-
Apoenzymes / metabolism
-
Binding Sites
-
Catalytic Domain*
-
Crystallography, X-Ray
-
Disks Large Homolog 4 Protein
-
Guanosine Monophosphate / metabolism
-
Guanylate Kinases
-
Intracellular Signaling Peptides and Proteins
-
Membrane Proteins
-
Models, Molecular
-
Molecular Sequence Data
-
Nerve Tissue Proteins / chemistry*
-
Nerve Tissue Proteins / metabolism*
-
Nucleoside-Phosphate Kinase / chemistry*
-
Nucleoside-Phosphate Kinase / metabolism*
-
Protein Binding
-
Protein Structure, Quaternary
-
Protein Structure, Secondary
-
Protein Structure, Tertiary
-
Rats
-
Sequence Alignment
-
Static Electricity
-
Structure-Activity Relationship
-
src Homology Domains*
Substances
-
Apoenzymes
-
Disks Large Homolog 4 Protein
-
Dlg4 protein, rat
-
Intracellular Signaling Peptides and Proteins
-
Membrane Proteins
-
Mpp2 protein, rat
-
Nerve Tissue Proteins
-
postsynaptic density proteins
-
Guanosine Monophosphate
-
Nucleoside-Phosphate Kinase
-
Guanylate Kinases