Nanodiscs separate chemoreceptor oligomeric states and reveal their signaling properties

Thomas Boldog, Stephen Grimme, Mingshan Li, Stephen G. Sligar, Gerald L. Hazelbauer

Research output: Contribution to journalArticle

Abstract

Bacterial chemoreceptors are transmembrane homodimers that can form trimers, higher order arrays, and extended clusters as part of signaling complexes. Interactions of dimers in oligomers are thought to confer cooperativity and cross-receptor influences as well as a 35-fold gain between ligand binding and altered kinase activity. In addition, higher order interactions among dimers are necessary for the observed patterns of assistance in adaptational modification among different receptors. Elucidating mechanisms underlying these properties will require defining which receptor functions can be performed by dimers and which require specific higher order interactions. However, such an assignment has not been possible. Here, we used Nanodiscs, an emerging technology for manipulating membrane proteins, to prepare small particles of lipid bilayer containing one or only a few chemoreceptor dimers. We found that receptor dimers isolated in individual Nanodiscs were readily modified, bound ligand, and performed transmembrane signaling. However, they were hardly able to activate the chemotaxis histidine kinase. Instead, maximal activation and thus full-range control of kinase occurred preferentially in discs containing approximately three chemoreceptor dimers. The sharp dependence of kinase activation on this number of receptors per dimer implies that the core structural unit of kinase activation and control is a trimer of dimers. Thus, our observations demonstrate that chemoreceptor transmembrane signaling does not require oligomeric organization beyond homodimers and implicate a trimer of dimers as the unit of downstream signaling.

Original languageEnglish (US)
Pages (from-to)11509-11514
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number31
DOIs
StatePublished - Aug 1 2006

Keywords

  • Membrane protein
  • Nanoparticle
  • Self-assembly
  • Transmembrane receptor
  • Transmembrane signaling

ASJC Scopus subject areas

  • General

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