NLRP3 is its own gatekeeper: a group hug of NLRP3 monomers controls inflammation

Iva Hafner-Bratkovič

doi:10.1016/j.tibs.2022.03.014

NLRP3 is its own gatekeeper: a group hug of NLRP3 monomers controls inflammation

Trends Biochem Sci. 2022 Aug;47(8):635-637. doi: 10.1016/j.tibs.2022.03.014. Epub 2022 Apr 2.

Author

Iva Hafner-Bratkovič¹

Affiliation

¹ Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, Ljubljana, 1000, Slovenia; EN-FIST Centre of Excellence, Trg Osvobodilne Fronte 13, Ljubljana, Slovenia. Electronic address: iva.hafner@ki.si.

PMID: 35382945
DOI: 10.1016/j.tibs.2022.03.014

Abstract

A recent study by Hochheiser et al. describes the cryo-electron microscopy (cryoEM) structure of an autoinhibited nucleotide-binding domain-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) decamer that assembles via LRR interactions and is further stabilized by the small-molecule NLRP3-specific inhibitor CRID3 binding into a cleft within the NACHT domain. The study provides a springboard for the development of novel NLRP3-based therapies.

Keywords: CRID3; Inflammasome; MCC950; NLRP3; inhibitor; oligomer.

Publication types

Research Support, Non-U.S. Gov't
Comment

MeSH terms

Cryoelectron Microscopy
Humans
Inflammasomes* / metabolism
Inflammation
NLR Family, Pyrin Domain-Containing 3 Protein*

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein