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

73 Scopus citations

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

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Keywords

  • MOLNEURO
  • PROTEINS
  • SIGNALING

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mishra, P., Socolich, M., Wall, M. A., Graves, J., Wang, Z., & Ranganathan, R. (2007). Dynamic Scaffolding in a G Protein-Coupled Signaling System. Cell, 131(1), 80-92. https://doi.org/10.1016/j.cell.2007.07.037