Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1
Year: 2018
Type: article
Abstract: Significance Inflammasomes are cytosolic protein complexes that detect the presence of pathogens and damages to elicit immune responses, and dysregulation in inflammasome signaling is associated with many human diseases. As the unified downstream effector of canonical inflammasomes, caspase-1 is recruited though CARD–CARD interactions with the adaptor proteins ASC or NLRC4. We have determined the cryo-EM structures of ASC CARD and NLRC4 CARD filaments. Using multidisciplinary methods, we reveal a common mechanism of caspase-1 CARD nucleation, assembly, and activation by equivalent assembly patterns in ASC and NLRC4. Collectively, our data provide insights into inflammasome assembly and activation and afford structural platforms for modulating these CARD–CARD interactions in potential therapeutic applications.
Institutions: Boston Children's Hospital, Harvard University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: Frederick National Laboratory for Cancer Research, National Institutes of Health, Harvard Digestive Diseases Center, Harvard University, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
OpenAlex ID: W2992534356