Structures of pattern recognition receptors reveal molecular mechanisms of autoinhibition, ligand recognition and oligomerization

Abstract

Pattern recognition receptors (PRRs) are essential sentinels for pathogens or tissue damage and integral components of the innate immune system. Recent structural studies have provided unprecedented insights into the molecular mechanisms of ligand recognition and signal transduction by several PRR families at distinct subcellular compartments. Here we highlight some of the recent discoveries and summarize the common themes that are emerging from these exciting studies. Better mechanistic understanding of the structure and function of the PRRs will improve future prospects of therapeutic targeting of these important innate immune receptors.

Figure 1

Ligand-binding and oligomerization of pattern recognition receptors TLR8 (A), NLRC4 (B), RIG-I (C), and AIM2 (D). The signaling, oligomerization, and ligand-binding domains are colored green, cyan and magenta except for the TLR8 ECD, which is in rainbow color from its N- to C-termini. Binding of small molecular agonist CL097 (in van der Waals spheres) induces close proximity of the TLR8 ECD C-termini and the cytoplasmic TIR domains (green) as shown in (A). Flagellin molecules are represented as orange ovals and the NAIP CARDs as green spheres in (B). The ADP/ATP molecules are shown as van der Waals spheres in (B-C). The NLRC4 inflammasome, RIG-I filament, and AIM2 inflammasome are represented schematically on the right side panels of (B-D).