Mismatched missiles

Part of the immune system that drills into invading bacteria and splits them open has been visualised in nanoscopic detail, with surprising results

Membrane attack complexes (MACs) are structures made of proteins that assemble in the body when an infection is detected. They latch on to the membranes of invading bacteria, such as meningitis, and punch a hole in them.

Eventually, if enough MACs punch a hole in the membrane, the bacteria will split open and die. MACs are of particular interest in cancer research, as some cancer cells are able to evade them.

In the new study, published in the journal Nature Communications, researchers from Cardiff University and Imperial College London and visualised the MAC using cryo-electron microscopy. This rapidly-advancing technique has the power to visualise complex protein structures at resolutions below a nanometre – one billionth of a metre.

The visualisation revealed a surprise. Instead of being a closed symmetric ring of proteins, as was expected by looking at similar protein structures, the MAC was revealed to have a ‘split-washer’ shape, where the ring was broken resulting in a mismatch of the symmetry.

Paul Morgan, Director of  Systems Immunity URI and Cardiff lead on the project said: "This new structure radically changes our understanding of how the MAC forms and opens new directions for research into how it works - particularly how it links to signalling pathways to cause cell activation, a subject of research in my group for over thirty years.”

“At the point where the ring splits and the symmetry is mismatched, the MAC doesn’t completely penetrate the bacteria membrane,” said study co-author Dr Doryen Bubeck from the Department of Life Sciences at Imperial.

“This opens up a whole new set of questions about its function. Is it sensing something about the membrane? Is it signalling other proteins?”