The dual PDZ domain from Postsynaptic density protein 95 forms a scaffold with peptide ligand

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  • External authors:
  • Nazahiyah Rodzli
  • C W Levy
  • J Chipperfield
  • L Bird

Abstract

PSD-95 is a member of Membrane Associated Guanylate Kinase class of proteins which form scaffolding interactions with partner proteins including ion and receptor channels. PSD-95 is directly implicated in modulating the electrical responses of excitable cells. The first two PSD-95/Disks Large/Zona Occludens (PDZ) domains of PSD-95 have been shown to be the key component in the formation of channel clusters. We report crystal structures of this dual domain in both in apo- and ligand-bound form; thermodynamic analysis of ligand association and Small Angle X-ray Scattering of the dual domain in the absence and presence of ligands. These experiments reveal that the ligated double domain forms a 3-dimensional scaffold which can be described by a Spacegroup. The concentration of the components in this study is comparable to those found in compartments of excitable cells such as the postsynaptic density and juxta-paranodes of Ranvier. These in vitro experiments inform the basis of the scaffolding function of PSD-95 and provide a detailed model for scaffold formation by the PDZ domains of PSD-95.

Bibliographical metadata

Original languageEnglish
JournalBiophysical Journal
Publication statusAccepted/In press - 16 Jun 2020

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