Interaction partners of PSD-93 studied by X-ray crystallography and fluorescence polarization spectroscopy

Research output: Contribution to journalJournal articleResearch

PSD-93 (chapsyn-110, DLG2) is a member of the family of membrane-associated guanylate kinase (MAGUK) proteins. The MAGUK proteins are involved in receptor localization and signalling pathways. The best characterized MAGUK protein, PSD-95, is known to be involved in NMDA receptor signalling via its PDZ domains. The PDZ domains of PSD-95 and PSD-93 are structurally very similar, but relatively little is known about the function of PSD-93. PSD-93 has been suggested to interact with GluD2 from the family of ionotropic glutamate receptors. Here, the interactions of four residues (GTSI) representing the extreme C-terminus of GluD2 with PSD-93 PDZ1 have been investigated in the crystalline phase. Two different binding modes of these residues were observed, suggesting that the peptide is not tightly bound to PSD-93 PDZ1. In accordance, the two N-terminal PSD-93 PDZ domains show no appreciable binding affinity for a GluD2-derived C-terminal octapeptide, whereas micromolar affinity was observed for a GluN2B-derived C-terminal octapeptide. This indicates that if present, the interactions between GluD2 and PSD-93 involve more than the extreme terminus of the receptor. In contrast, the tumour-suppressor protein SCRIB PDZ3 shows low micromolar affinity towards the GluD2-derived octapeptide, which is in agreement with previous findings using high-throughput assays.
Original languageEnglish
JournalActa Crystallographica. Section D: Biological Crystallography
Issue numberPt 4
Pages (from-to)587-94
Number of pages8
Publication statusPublished - Apr 2013

    Research areas

  • Cell Communication, Crystallization, Crystallography, X-Ray, Fluorescence Polarization, Guanylate Kinase, Humans, Microscopy, Fluorescence, Multiphoton, Peptide Fragments, Protein Interaction Mapping, Protein Structure, Tertiary, Spectrometry, Fluorescence, Tumor Suppressor Proteins

ID: 74768301