PerspectiveStructural Biology

Assembling the wheel of death

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Science  23 Oct 2015:
Vol. 350, Issue 6259, pp. 376-377
DOI: 10.1126/science.aad3981

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Inflammation is an essential defense strategy mounted by the innate immune system to eradicate infections and repair tissue damage. The inflammasome is an intracellular signaling complex involved in inflammation initiation and perpetuation. These multimeric protein assemblies promote the activation of proteases and the maturation of proinflammatory cytokines, as well as a form of cell death (pyroptosis) that incites further inflammation (1). Excessive inflammasome activation has been implicated in chronic inflammatory disorders such as diabetes, atherosclerosis, multiple sclerosis, and Alzheimer's disease (2). However, inflammasomes also play protective roles in response to microbial pathogens. On pages 404 and 399 of this issue, Zhang et al. (3) and Hu et al. (4) report the structural basis for activation of an inflammasome implicated in both infectious disease response and autoinflammatory disorders (see the first figure).