Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor

Francis Lister, Bryden Le Bailly, Simon J. Webb*, Jonathan Clayden

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

104 Citations (Scopus)
654 Downloads (Pure)

Abstract

Signal transduction through G protein-coupled receptors (GPCRs) involves binding to signalling molecules at the cell surface, which leads to global changes in molecular conformation that are communicated through the membrane. Artificial mechanisms for communication involving ligand binding and global conformational switching have been demonstrated so far only in the solution phase. Here we report a membrane-bound synthetic receptor that responds to binding of a ligand by undergoing a conformational change that is propagated over several nanometres, deep into the phospholipid bilayer. Our design uses a helical foldamer core, with structural features borrowed from a class of membrane-active fungal antibiotics, ligated to a water-compatible, metal-centred binding site and a conformationally-responsive fluorophore. Using the fluorophore as a remote reporter of conformational change, we find that binding of specific carboxylate ligands to a Cu(II) cofactor at the binding site perturbs the foldamer's global conformation, mimicking the conformational response of a GPCR to ligand binding.
Original languageEnglish
Pages (from-to)420–425
Number of pages6
JournalNature Chemistry
Volume9
Issue number5
Early online date6 Mar 2017
DOIs
Publication statusPublished - May 2017

Research Groups and Themes

  • Bristol BioDesign Institute

Keywords

  • synthetic biology

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