Projects per year
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 language | English |
---|---|
Pages (from-to) | 420–425 |
Number of pages | 6 |
Journal | Nature Chemistry |
Volume | 9 |
Issue number | 5 |
Early online date | 6 Mar 2017 |
DOIs | |
Publication status | Published - May 2017 |
Research Groups and Themes
- Bristol BioDesign Institute
Keywords
- synthetic biology
Fingerprint
Dive into the research topics of 'Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor'. Together they form a unique fingerprint.Projects
- 2 Finished
-
A 13C NMR Coldprobe to Underpin Chemistry Research.
Butts, C. P. (Principal Investigator)
28/02/14 → 29/11/17
Project: Research
-
3-month Core Capability for Chemistry Research
Crosby, J. (Principal Investigator)
1/01/13 → 1/04/13
Project: Research