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Figure 2
The Glu–Arg–Asp charge relay as an NLRP conformational regulation element. (a) Sequence alignment of all 14 NLR PYDs. The secondary-structure elements α1–α6 are indicated. The conserved hydrophobic core residues are highlighted in grey. Additionally, the solvent-exposed hydrophobic residues Trp72, Leu76 and Leu87 are coloured magenta. Brackets indicate the NLRP13-specific insertion of residues Leu41–Gln49. (b) Close-up of the consensus of Glu26, Asp86 and the alternative conformational regulation element (CRE) M82NL84 or M82NR84. Both Glu26 and Asp86 are necessary for the charge bridge with the MNR motif. (c) The crystal structure of NLRP14 PYD L84R (cyan) superimposed onto that of wild-type NLRP14 PYD (pink). The L84R mutant adopts a closed conformation; the intact charge bridge is highlighted. |