1. Schematic summary of innate signaling pathway components and filaments.
Schematic summary of innate signaling pathway components and filaments. In this schematic, example signaling domains are distinguished by shape. LRR domains are stacks of ellipses; TIR domains are circles; death domains and CARD domains are rectangles; PYRIN domains are triangles. Filaments and assemblies are elongated cylinders. (A) TLR signaling via MyD88. The example shows dimerization of TLR4 (and coreceptor MD-2) by bacterial LPS. Signaling is via TIR domain interactions and the MyD88 IRAK kinase death domain assembly: the MyDDosome (blue/green). (B) TLR signaling via TRIF. TRIF is a TIR-domain containing adaptor for TLR signaling from endosomes. The TRIF N-terminal domain "TriFFosome" assembly (gray) is speculative. (C) NLR signaling via the inflammasome and ASC. The example is assembly of NLRP3 into the inflammasome together with caspase 1 and the adaptor ASC. ASC pyrin domains also self-assemble as filaments (dark red). (D) Recognition of viral RNA by RLRs. RIG-I and MDA5 are CARD-domain containing ATP-helicases that bind double-stranded RNA. RIG-I specifically recognizing triphosphate (ppp) 5′ ends. CARD domains of helicases on longer RNA self-assemble into tetramers that interact with the MAVS protein. (E) MAVS signaling. MAVS CARD domains are displayed at the outer membrane of mitochondria. The MAVS CARD associates with the RLR helicase CARDs and also produces filaments (magenta). (F) CLR signaling. Dectin-1 is an example in which dimerization activates kinases and signals via the CARD9, Bcl10, and the death-domain containing paracaspase MALT1 to mediate NFκB activation. Bcl10 also forms filamentous assemblies (gray/black).
Clare E. Bryant et al. Pharmacol Rev 2015;67:
Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics