Fig. 6. Transition of NLRP3^PYD nucleation seeds to ASC^PYD filament elongation.

(A) Cartoon of the filament transition from the nucleation seed NLRP3^PYD to the elongation adaptor ASC^PYD. The transition interface of the heteromeric PYD interactions is indicated. (B) Electrostatic surface potential of the complementary filaments from the ASC^PYD A-end and the NLRP3^PYD B-end, displayed from −4 Boltzmann constant (k_BT) (red) to +4 k_BT (blue). (C) Sequence alignment of the ASC and NLRP3 PYDs with the interface residues highlighted. Interacting residues from the a-side interfaces in ASC and the b-side interfaces in NLRP3 are colored as before. (D) Close-up images of the interactions in the three interface types I, II, and III for the energy-minimized transition interface between the NLRP3^PYD filament (light blue) and the ASC^PYD filament (green). Salt bridges (types I and III) and hydrogen bonds (type II) are indicated by dashed lines. (E) Model of an ASC filament (green) elongating on the NLRP3^PYD filament nucleation seed (light blue). Whereas the PYD domain of ASC forms the filamentous stem structure, the CARD domain could adopt variable compositions at the surface of the filament.