Figure 2.

AMPs and amyloids organize immune ligands into spatially periodic nanocomplexes to amplify TLR activation. (A) LL37 self-assembles into a 4-fold amyloid-like superhelical protofibril in the presence of DNA. Hydrophobic residues are buried in the interior of the protofibril while cationic residues are exposed at the perimeter. (B) Structure of the LL37-DNA complex showing cross linking of spatially periodic DNA strands by LL37 protofibrils at an inter-DNA spacing of 3.40 nm, which is optimal for TLR9 binding and amplification of cytokine production. (C) End-on view and (D) top-down view of geometrically organized DNA immune complexes binding to clustered TLR9 in the endosomal membrane. In addition to the LL37-DNA complex, CXCL4-DNA complexes formed in scleroderma and curli-DNA complexes from Salmonella biofilms also demonstrate similar structural properties that enable amplification of TLR9 in immune cells and type I interferon production. (A,B) are adapted with permission from (4). (C,D) are adapted with permission from (44) and (10).