Inflammasomes are multiprotein platforms that initiate innate immunity by recruitment and activation of caspase-1. The NLRP1B inflammasome is activated upon direct cleavage by the anthrax lethal toxin protease. However, the mechanism by which cleavage results in NLRP1B activation is unknown. In this study, we find that cleavage results in proteasome-mediated degradation of the amino-terminal domains of NLRP1B, liberating a carboxyl-terminal fragment that is a potent caspase-1 activator. Proteasome-mediated degradation of NLRP1B is both necessary and sufficient for NLRP1B activation. Consistent with our functional degradation model, we identify IpaH7.8, a Shigella flexneri ubiquitin ligase secreted effector, as an enzyme that induces NLRP1B degradation and activation. Our results provide a unified mechanism for NLRP1B activation by diverse pathogen-encoded enzymatic activities.

Systematic analysis of related compounds is crucial to the design of single-molecule magnets with improved properties, yet such studies on multinuclear lanthanide complexes with strong magnetic coupling remain rare. Herein, we present the synthesis and magnetic characterization of the series of radical-bridged dilanthanide complex salts [(Cp*₂Ln)₂(μ-5,5'-R₂bpym)](BPh₄) (Ln = Gd, Dy; R = NMe₂ (1), OEt (2), Me (3), F (4); bpym = 2,2'-bipyrimidine). Modification of the substituent on the bridging 5,5'-R₂bpym radical anion allows the magnetic exchange coupling constant, J_Gd-rad, for the gadolinium compounds in this series to be tuned over a range from -2.7 cm^-1 (1) to -11.1 cm^-1 (4), with electron-withdrawing or -donating substituents increasing or decreasing the strength of exchange coupling, respectively. Modulation of the exchange coupling interaction has a significant impact on the magnetic relaxation dynamics of the single-molecule magnets 1-Dy through 4-Dy, where stronger J_Gd-rad for the corresponding Gd³⁺ compounds is associated with larger thermal barriers to magnetic relaxation (U_eff), open magnetic hysteresis at higher temperatures, and slower magnetic relaxation rates for through-barrier processes. Further, we derive an empirical linear correlation between the experimental U_eff values for 1-Dy through 4-Dy and the magnitude of J_Gd-rad for the corresponding gadolinium derivatives that provides insight into the electronic structure of these complexes. This simple model applies to other organic radical-bridged dysprosium complexes in the literature, and it establishes clear design criteria for increasing magnetic operating temperatures in radical-bridged molecules.