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The commitment of Vall d'Hebron University Hospital to innovation allows us to be at the forefront of medicine, providing first class care adapted to the changing needs of each patient.
Speaker: Dr. Pablo Pelegrín, Scientific Deputy Director & Principal Investigator, BioMedical Research Institute of Murcia - Department of Biochemistry and Molecular Biology B and Immunology-Faculty of Medicine-University of Murcia
The NLRP3 inflammasome is activated in response to a wide range of stimuli and drives diverse inflammatory diseases. The decrease of intracellular K+ concentration is a minimal upstream signal to most of the different NLRP3 activation models. Here we found that cellular K+ efflux induces a stable structural change in the inactive NLRP3 promoting an open conformation as a step preceding activation. This conformational change is facilitated by the presence of the specific NLRP3 FISNA domain and a unique flexible linker sequence between the PYD and FISNA domains. This linker is also important to facilitate the ensemble of NLRP3PYD into a seed structure for ASC oligomerization. The introduction of the NLRP3 PYD-linker-FISNA sequence into NLRP6 resulted in a chimeric receptor able to be activated by K+ efflux-specific NLRP3 activators and promoted an in vivo inflammatory response to uric acid crystals. Our results establish that the N-terminal sequence between PYD and NACHT domain of NLRP3 is key for inflammasome activation.
Host: Dr. Miguel Segura Ginard, Senior researcher- Childhood Cancer and Blood Disorders (VHIR)
Register here to attend by Zoom: https://gencat.zoom.us/j/93529101286
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