Ligand-modulated conformational switching in a fully synthetic membrane-bound receptorCitation formats

  • Authors:
  • Francis Lister
  • Bryden Le Bailly
  • Simon Webb
  • Jonathan Clayden

Standard

Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor. / Lister, Francis; Le Bailly, Bryden; Webb, Simon; Clayden, Jonathan.

In: Nature Chemistry, Vol. 9, 2017, p. 420-425.

Research output: Contribution to journal › Article › peer-review

Harvard

Lister, F, Le Bailly, B, Webb, S & Clayden, J 2017, 'Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor', Nature Chemistry, vol. 9, pp. 420-425. https://doi.org/10.1038/nchem.2736

APA

Lister, F., Le Bailly, B., Webb, S., & Clayden, J. (2017). Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor. Nature Chemistry, 9, 420-425. https://doi.org/10.1038/nchem.2736

Vancouver

Lister F, Le Bailly B, Webb S, Clayden J. Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor. Nature Chemistry. 2017;9:420-425. https://doi.org/10.1038/nchem.2736

Author

Lister, Francis ; Le Bailly, Bryden ; Webb, Simon ; Clayden, Jonathan. / Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor. In: Nature Chemistry. 2017 ; Vol. 9. pp. 420-425.

Bibtex

@article{a793fab101db4d4f98453abd2303bfe0,
title = "Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor",
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.  ",
author = "Francis Lister and {Le Bailly}, Bryden and Simon Webb and Jonathan Clayden",
year = "2017",
doi = "10.1038/nchem.2736",
language = "English",
volume = "9",
pages = "420--425",
journal = "Nature Chemistry",
issn = "1755-4330",
publisher = "Springer Nature",

}

RIS

TY - JOUR

T1 - Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor

AU - Lister, Francis

AU - Le Bailly, Bryden

AU - Webb, Simon

AU - Clayden, Jonathan

PY - 2017

Y1 - 2017

N2 - 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.  

AB - 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.  

U2 - 10.1038/nchem.2736

DO - 10.1038/nchem.2736

M3 - Article

VL - 9

SP - 420

EP - 425

JO - Nature Chemistry

JF - Nature Chemistry

SN - 1755-4330

ER -