Abstract

While cryo-EM has transformed our view of the structures of protein assemblies, behind the scenes gas phase structural biology has been emerging. Over a number of decades mass spectrometrists have revealed that the folding and topology of protein complexes can be retained in the gas phase, if appropriate experimental parameters are applied. These discoveries led to early compelling studies of antibody-antigen complexes, viruses, ribosomes and molecular chaperones. More recently ‘snapshots’ of membrane protein complexes in the gas phase have been particularly enlightening. Widely considered the most challenging of protein complexes, but yet the most important given their physiological roles, the gas phase turns out to be an excellent medium in which to interrogate hydrophobic membrane proteins. When encased in detergent micelles, or other membrane mimetics, the effects of lipids on stability, conformational change, dynamics and protein interactions are revealed. As such, mass spectrometry is informing membrane embedded efflux pumps (often implicated in antibiotic resistance mechanisms) assembly of membrane protein interfaces (primarily in solute carriers) and receptor mediated signalling pathways (typically of GPC Rs). In this lecture I will trace the history of these developments using selected highlights to illustrate progress made to date. Finally, I will describe exciting future developments – soon to be realised…..