ABS 105: Biochemical Mechanisms of Pyrin Inflammasome Activation

Luochen Liu ² ³ , Audrey Lessing ¹ ³ , Hao Wu ² ³

¹ Northeastern University, MA, USA
² Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
³ Program in Cellular and Molecular Medicine, Boston Children's Hospital.

Van Wickle (2025) Volume 1, ABS 105

Introduction: The inflammasome pathway is a crucial player of the innate immune system by triggering inflammatory responses, including the secretion of pro-inflammatory cytokines to recruit immune cells to the site of infection. The pyrin sensor initiates an inflammasome signaling pathway in response to pathogen-induced disturbances in the actin cytoskeleton. Once activated, the sensor forms an oligomer via its PYD domain, leading to the recruitment of downstream signaling factors. Notably, pyrin mutations are linked to diseases, such as Familial Mediterranean Fever (FMF), which is the most common autoinflammatory disease. Here, we report a cryo-EM structure of the pyrin PYD filament, whose assembly is mediated by six asymmetric interfaces. Mutations of these interfaces were performed and nanobody testing is the subsequent step.