title: Self-oligomerization of ASC PYD domain prevents the assembly of inflammasome in vitro.
abstract: NALP3 inflammasome, which is an inflammatory caspase-activating complex, is composed of three proteins: NALP3 (an NOD-like receptor), an apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1. NALP3 senses danger signals, while ASC is an adaptor molecule containing two protein interaction modules: pyrin domain (PYD) and caspase recruitment domain (CARD). Caspase-1 is a cysteine protease that uses cysteine as a nucleophile and has a CARD domain for protein interaction. During inflammasome formation, the ASC adaptor acts as a bridge between caspase and NOD-like receptor (NLR) by offering the CARD for CARD-CARD interactions and PYD for PYD-PYD interactions. In the current study, we successfully purified and characterized NALP3 PYD and ASC PYD. The results showed that ASC PYD easily self-oligomerized under physiological conditions, and this self-oligomerization of the ASC PYD prevented complex formation with NALP3 PYD in vitro.
authors.affiliation: Department of Biochemistry, School of Biotechnology and Graduate School of Biochemistry, Yeungnam University, Gyeongsan, South Korea.
authors.forename: Kannan Badri
authors.initials: KB
authors.lastname: Narayanan
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Jang
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000737:chemistry*; D003598:Cytoskeletal Proteins / Q000737:chemistry*; D006801:Humans; D058847:Inflammasomes / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C402202:PYCARD protein, human