Dynamic Scaffolding in a G Protein-Coupled Signaling System

Prashant Mishra, Michael Socolich, Mark A. Wall, Jennifer Graves, ZiFen Wang, Rama Ranganathan

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

The INAD scaffold organizes a multiprotein complex that is essential for proper visual signaling in Drosophila photoreceptor cells. Here we show that one of the INAD PDZ domains (PDZ5) exists in a redox-dependent equilibrium between two conformations-a reduced form that is similar to the structure of other PDZ domains, and an oxidized form in which the ligand-binding site is distorted through formation of a strong intramolecular disulfide bond. We demonstrate transient light-dependent formation of this disulfide bond in vivo and find that transgenic flies expressing a mutant INAD in which PDZ5 is locked in the reduced state display severe defects in termination of visual responses and visually mediated reflex behavior. These studies demonstrate a conformational switch mechanism for PDZ domain function and suggest that INAD behaves more like a dynamic machine rather than a passive scaffold, regulating signal transduction at the millisecond timescale through cycles of conformational change.

Original languageEnglish (US)
Pages (from-to)80-92
Number of pages13
JournalCell
Volume131
Issue number1
DOIs
StatePublished - Oct 5 2007

Fingerprint

PDZ Domains
GTP-Binding Proteins
Disulfides
Multiprotein Complexes
Signal transduction
Scaffolds (biology)
Scaffolds
Conformations
Photoreceptor Cells
Binding Sites
Switches
Ligands
Diptera
Defects
Drosophila
Oxidation-Reduction
Reflex
Signal Transduction
Light

Keywords

  • MOLNEURO
  • PROTEINS
  • SIGNALING

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Dynamic Scaffolding in a G Protein-Coupled Signaling System. / Mishra, Prashant; Socolich, Michael; Wall, Mark A.; Graves, Jennifer; Wang, ZiFen; Ranganathan, Rama.

In: Cell, Vol. 131, No. 1, 05.10.2007, p. 80-92.

Research output: Contribution to journalArticle

Mishra, Prashant ; Socolich, Michael ; Wall, Mark A. ; Graves, Jennifer ; Wang, ZiFen ; Ranganathan, Rama. / Dynamic Scaffolding in a G Protein-Coupled Signaling System. In: Cell. 2007 ; Vol. 131, No. 1. pp. 80-92.
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