Protein aggregation or liberation during cell necrosis

What is it about?

Proteins have a natural shape which if lost causes them to aggregate into toxic molecules … but is this always the case? We have used state-of-the-art mass spectrometry and microscopy to characterise a different kind of protein aggregation that instead helps the body cope with injury. Indeed, this unique type of protein aggregation called ‘Nucleocytoplasmic Coagulation’ may minimise the risk of autoimmune disease after injury. This discovery challenges the dogma that protein aggregation is invariably toxic.

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Why is it important?

We have profiled the intracellular proteins that aggregate during necrotic injury. Our data shows that: (i) protein aggregation during necrosis is distinguishable from canonical amyloidogenesis, and (ii) that physicochemical features such as cysteine content influence whether a protein is retained or released from necrotic cells. For instance, proteins which low cysteine content are more likely to avoid aggregation and instead be released into the extracellular milieu upon necrosis. Intriguingly, many of these "released" proteins are also known autoantigens. Accordingly, we hypothesis that protein aggregation during necrosis is a favourable event that mitigates autoimmunity. It is hoped that by harnessing this unique kind of protein aggregation, we can devise new ways to help the body recuperate from injury in a way that prevents subsequent autoimmune disease.