Extended Data Fig. 7: Arrangements of the trLRR and the cnLRR.
From: Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3
a, Sequence alignment of individual repeats of the LRR domain. The trLRR starts at position F650 with the FXXIXI motif and a 26-aa repeat. An LRR-mismatching region of 42 residues interrupts the conventional fold from residue F683 on, forming a flexible, acidic loop. A highly charged stretch of 14 residues (689–702, theoretical pI 4.4) with acidic residues at the tip binds into the concave side of the LRR. The cnLRR starts at position L743 and contains 10 repeats of a proto-typic 28/29 residue alteration49. Charged residues in the concave surface of the LRR are coloured blue and red. Leucine residues or homologous hydrophobic residues at LRR-defining positions are indicated bold, and cysteines are boxed yellow. Mismatching residues that preclude a cnLRR fold are boxed cyan. Secondary structure elements of a cnLRR fold are indicated at the top. b, Electrostatics of the LRR–acidic loop–LRR’ interaction. On the left side is the acidic loop interaction in the LRR without the loop (650–1036, Δ683–727) shown. On the right is the interaction of the C-terminal repeat (998’-1036’) of the cognate LRR binding into the concave LRR side shown.
