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

Michael L. Reese, Srikanth Dakoji, David S. Bredt, Volker Dötsch

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)155-163
Number of pages9
JournalNature Structural and Molecular Biology
Volume14
Issue number2
DOIs
StatePublished - Feb 1 2007

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'The guanylate kinase domain of the MAGUK PSD-95 binds dynamically to a conserved motif in MAP1a'. Together they form a unique fingerprint.

  • Cite this