Membrane pores: from structure and assembly, to medicine and technology

Biological membranes are essential barriers, defining and protecting living cells. Pore-forming proteins (PFPs) are recognized as important players in infection and immunity and target membranes by opening up channels through them. They achieve this by converting from a form that is soluble in aqueous solution to one that is inserted into a membrane. Therefore, they must adopt two different structures with one converting into the other during membrane attack. During this conversion, individual PFP subunits usually self-associate into higher-order assemblies with which lipid molecules may be associated. Over the last 25 years, the biology of membranes and membrane proteins, including PFPs, has undergone a remarkable maturation. We now understand far better than we did how soluble proteins can convert themselves into membrane-inserted pore-forming assemblies by refolding from one stable topology to another, by mechanisms that differ remarkably in detail. The papers published in this issue arise from a Royal Society Discussion Meeting held in June 2016. The aim of the meeting was to look at the physical basis of membrane pore formation from both the perspective of the protein making the attack and that of the lipid bilayer being targeted. Our aim was to reset the debate on how PFPs work, seeking areas of commonality and giving research in the field a new momentum. A second aim was to place investigations of PFPs in a biomedical context. The sense of the meeting was clearly that these aims were achieved, and this was reflected in the final talk of the meeting, which was given by Dame Carol Robinson. Her perspective as a biophysical chemist working with membrane-associated proteins and protein–lipid interactions brought an invaluable oversight to our discussions. In her presentation, Professor Robinson reviewed ways in which native mass spectrometry, in particular, has proved a very powerful way to interrogate protein–protein …