Fig. 6. Modeled specific interfaces of the CARD8-CT and NLRP1-CT filaments for caspase-1 and ASC, respectively.
a, b Opposing arrangements of CARD8 and caspase-1 in their hypothetical modes of interaction. The electrostatic surfaces indicate that the negatively charged Type b surface of CARD8 most likely matches the positively charged Type a surface of caspase-1 in a. c, d Opposing arrangements of NLRP1 and ASC in their hypothetical modes of interaction. The electrostatic surfaces indicate that the largely negatively charged Type b surface of NLRP1 most likely matches the positively charged Type a surface of ASC in c. e Detailed modeled CARD-CARD type I–III interactions between CARD8 (green) and caspase-1 (gold). f Detailed modeled CARD-CARD type I–III interactions between NLRP1 (green) and ASC (gold). g Simplified illustration of NLRP1 and CARD8 hierarchy in inflammasome signaling. NLRP1 recruits ASC, followed by capase-1 recruitment. In contrast, CARD8 can only recruit caspase-1 directly. In a–f, the inflammasome sensors NLRP1 and CARD8 are colored turquoise while the downstream molecules ASC and caspase-1 are colored brown.