title: Interaction partners of PSD-93 studied by X-ray crystallography and fluorescence polarization spectroscopy.
abstract: 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.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Monica
authors.initials: M
authors.lastname: Fiorentini
authors.forename: Anders
authors.initials: A
authors.lastname: Bach
authors.forename: Kristian
authors.initials: K
authors.lastname: Strømgaard
authors.forename: Jette S
authors.initials: JS
authors.lastname: Kastrup
authors.forename: Michael
authors.initials: M
authors.lastname: Gajhede
mesh_terms: D002450:Cell Communication / Q000502:physiology; D003460:Crystallization; D018360:Crystallography, X-Ray; D005454:Fluorescence Polarization; D051528:Guanylate Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D036641:Microscopy, Fluorescence, Multiphoton; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D025521:Tumor Suppressor Proteins; C496468:DLG2 protein, human; D051528:Guanylate Kinases
keywords: GluN2B and GluD2 C-terminal tails; PDZ domains; PDZ1; PSD-93