G protein-coupled receptors (GPCRs) are key drug targets and important signaling proteins embedded in cell membranes. To study the proteins’ specific signaling interactions more easily by eliminating the complexities of the cellular environment, researchers often use detergents to extract them from cell membranes and then reconstitute the receptors in synthetic membranes. The detergents can modify ligand binding interactions and other native properties of GPCRs, so researchers must use dialysis or adsorbents to remove detergents before studying the reconstituted proteins. A team led by Neal Devaraj and Roger Sunahara of the University of California, San Diego, developed a GPCR reconstitution technique that doesn’t require detergent cleanup (J. Am. Chem. Soc. 2017, DOI: 10.1021/jacs.6b12830). In the technique, called in situ lipid synthesis for protein reconstitution technology (INSYRT), the scientists use acyl maltose thioesters to extract GPCRs from cells, forming micelles containing the proteins. They then use native chemical ligation to combine acyl groups in the micelles with lysolipids, forming phospholipids that assemble spontaneously into spherical GPCR-containing proteoliposomes. The thioesters don’t survive the reaction and therefore don’t have to be removed. In a presentation at the ACS meeting, Devaraj showed that INSYRT could reconstitute the adenosine A2A receptor in proteoliposomes, where the receptor maintained its natural function.