Functional relevance of the disulfide-linked complex of the N-terminal PDZ domain of InaD with NorpA

Michelle E. Kimple, David P. Siderovski, John Sondek

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

In Drosophila, phototransduction is mediated by Gq-activation of phospholipase C and is a well studied model system for understanding the kinetics of signal initiation, propagation and termination controlled by G proteins. The proper intracellular targeting and spatial arrangement of most proteins involved in fly phototransduction require the multi-domain scaffolding protein InaD, composed almost entirely of five PDZ domains, which independently bind various proteins including NorpA, the relevant phospholipase C-β isozyme. We have determined the crystal structure of the N-terminal PDZ domain of InaD bound to a peptide corresponding to the C-terminus of NorpA to 1.8 Å resolution. The structure highlights an intermolecular disulfide bond necessary for high affinity interaction as determined by both in vitro and in vivo studies. Since other proteins also possess similar, cysteine-containing consensus sequences for binding PDZ domains, this disulfide-mediated 'dock-and-lock' interaction of PDZ domains with their ligands may be a relatively ubiquitous mode of coordinating signaling pathways.

Original languageEnglish
Pages (from-to)4414-4422
Number of pages9
JournalEMBO Journal
Volume20
Issue number16
DOIs
StatePublished - 15 Aug 2001

Keywords

  • Disulfide bond
  • InaD
  • PDZ domain
  • Phospholipase C-β
  • Scaffolding protein

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