title: The structure of the CARD8 caspase-recruitment domain suggests its association with the FIIND domain and procaspases through adjacent surfaces.
abstract: CARD8 plays crucial roles in regulating apoptotic and inflammatory signaling pathways through the association of its caspase-recruitment domain (CARD) with those of procaspase-9 and procaspase-1. The CARD8 CARD has also been predicted to form an intramolecular complex with its FIIND domain. Here, the first crystal structure of the CARD8 CARD is reported; it adopts a six-helix bundle fold with a unique conformation of the α6 helix that is described here for the first time. The surface of the CARD8 CARD displays a prominent acidic patch at its α2, α3 and α5 helices that may interact with the procaspase-9 CARD, whereas an adjacent charged surface at its α3 and α4 helices may associate with the CARD8 FIIND domain without interfering with the CARD-CARD interaction. This suggests that the function of CARD8 may be regulated by both intramolecular and intermolecular interactions involving electrostatic attractions.
authors.affiliation: Structural Immunobiology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0430, USA.
authors.forename: Tengchuan
authors.initials: T
authors.lastname: Jin
authors.forename: Mo
authors.initials: M
authors.lastname: Huang
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: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000737:chemistry* / Q000378:metabolism; D020170:Caspase 1 / Q000737:chemistry* / Q000378:metabolism; D053453:Caspase 9 / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013499:Surface Properties; D014961:X-Ray Diffraction
chemical_list: D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D009363:Neoplasm Proteins; D053453:Caspase 9; D020170:Caspase 1
keywords: CARD8; CARDs; death-domain fold; electrostatic attraction