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Nat Struct Mol Biol. 2007 Feb;14(2):155-63. Epub 2007 Jan 14.

The guanylate kinase domain of the MAGUK PSD-95 binds dynamically to a conserved motif in MAP1a.

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Graduate Group in Biophysics, University of California, San Francisco, California 94143, USA.


The postsynaptic density protein PSD-95 and related membrane-associated guanylate kinases are scaffolding proteins, whose modular interaction motifs organize protein complexes at cell junctions. The signature guanylate kinase domain (GK) contains elements of the protein's GMP-binding site but does not bind nucleotide. Instead, the GK domain has evolved from an enzyme to a protein-protein interaction motif. Here, we show that this canonical GMP-binding region interacts with microtubule-associated protein-1a (MAP1a) and we present a structural model. We determine the consensus GK-binding sequence in MAP1a and demonstrate that PSD-95 can use a similar interaction mode to bind diverse protein partners. Furthermore, we show that PSD-95 GK has adopted the conformational flexibility of the ancestral enzyme to bind its varied ligands, which suggests a mechanism of regulation.

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