Interaction partners of PSD‐93 studied by X‐ray crystallography and fluorescence polarization spectroscopy. (24th March 2013)

• Record Type: Journal Article
• Authors: Fiorentini, Monica; Bach, Anders; Strømgaard, Kristian; Kastrup, Jette S.; Gajhede, Michael
• Is Part Of: Acta crystallographica. Volume 69:Part 4(2013:Apr.)
• Page Start: 587
• Page End: 594
• Publication Date: 2013-03-24
• Subjects: PSD‐93 -- PDZ domains -- PDZ1 -- GluN2B and GluD2 C‐terminal tails; Biomolecules -- Structure -- Periodicals; Physical biochemistry -- Periodicals; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; 572
• DOI: 10.1107/S0907444912051839
• Languages: English
• ISSNs: 0907-4449

Abstract

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.