title: Structure of the NLRP1 caspase recruitment domain suggests potential mechanisms for its association with procaspase-1.
abstract: The NLRP1 inflammasome responds to microbial challenges such as Bacillus anthracis infection and is implicated in autoimmune disease such as vitiligo. Human NLRP1 contains both an N-terminal pyrin domain (PYD) and a C-terminal caspase recruitment domain (CARD), with the latter being essential for its association with the downstream effector procaspase-1. Here we report a 2.0 Å crystal structure of the human NLRP1 CARD as a fusion with the maltose-binding protein. The structure reveals the six-helix bundle fold of the NLRP1 CARD, typical of the death domain superfamily. The charge surface of the NLRP1 CARD structure and a procaspase-1 CARD model suggests potential mechanisms for their association through electrostatic attraction.
authors.affiliation: Structural Immunobiology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0430, USA.
authors.forename: Tengchuan
authors.initials: T
authors.lastname: Jin
authors.forename: James
authors.initials: J
authors.lastname: Curry
authors.forename: Patrick
authors.initials: P
authors.lastname: Smith
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Jiang
authors.forename: T Sam
authors.initials: TS
authors.lastname: Xiao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry*; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry*; D020170:Caspase 1 / Q000737:chemistry*; D020169:Caspases / Q000737:chemistry; D006801:Humans; D000070576:NLR Proteins; D011485:Protein Binding; D060066:Protein Interaction Maps; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D020169:Caspases; D020170:Caspase 1