Department of Chemistry

Department of Chemistry University of Oxford

Mass spectrometry uncovers a novel lipid that mediates signalling between GPCRs and G-proteins

Mass spectrometry uncovers a novel lipid that mediates signalling between GPCRs and G-proteins

This week in Nature researchers from the Robinson group report the first transmission into the gas phase of intact complexes formed between GPCRs and G-proteins. Yen et al used mass spectrometry to reveal the presence of a novel lipid (PIP2) that stabilises interactions within these complexes. Supported by site directed mutagenesis and computation from Mark Sansom's group they located the lipid binding site on the intracellular leaflet and showed how it stabilised the interaction by bridging between the receptor and a particular G-α subunit. Overall therefore they have uncovered a new mechanism that enhances selective coupling of receptors, significant for understanding many aspects of diseases and important for drug discovery.

The illustration shows a G-protein coupled receptor (blue) in a membrane (grey) is 'stapled' to its cognate G protein (orange) via PIP2 lipids (green). This enhanced coupling in the presence of PIP2 was discovered by preserving these interactions by means of electrospray mass spectrometry. more........