Fig. 7. Schematic representation of the proposed activation mechanism of human NLRP3.

From an inactive, resting state (1) the protein is turned, for example, by reversible PTMs such as phosphorylation, into a primed state (2) characterized by loss of autoinhibition. This state is capable of ATP uptake, which converts the protein to an active state (3). The ability of intrinsic ATP hydrolysis allows the protein to relapse to its resting or primed state. The active protein is eventually able to assemble into a quaternary structure, state (4), competent for downstream signaling, such as the induction of ASC filament formation.