Regulation of signaling by cooperative assembly formation in mammalian innate immunity signalosomes by molecular mimics. (March 2020)

• Record Type: Journal Article
• Authors: Nanson, Jeffrey D.; Rahaman, Md. Habibur; Ve, Thomas; Kobe, Bostjan
• Is Part Of: Seminars in cell & developmental biology. Volume 99(2020)
• Page Start: 96
• Page End: 114
• Publication Date: 2020-03
• Subjects: CARD caspase recruitment domain -- COP CARD-only protein -- cryo-EM cryo-electron microscopy -- DAMP danger-associated molecular pattern -- DD death domain -- DED death effector domain -- MLKL mixed lineage kinase domain-like protein -- NBD nucleotide-binding domain -- NLR nucleotide binding and oligomerization domain (NOD), leucine-rich repeat (LRR)-containing/NOD-like receptor -- PAMP pathogen-associated molecular pattern -- POP PYD-only protein -- PRR pattern recognition receptor -- PYD pyrin domain -- RHIM RIP homotypic interaction motif -- RIP receptor-interacting protein -- RLR RIG-I-like receptor -- SCAF signaling by cooperative assembly formation -- Tcp bacterial TIR domain-containing protein -- TIR domain Toll/interleukin-1 receptor domain -- TLR Toll-like receptor -- TNF tumor necrosis factor -- BIR baculovirus inhibitior of apoptosis protein repeat -- MDA5 melanoma differentiation associated factor 5 -- PDB Protein Data Bank -- RIG-I retinoic acid-inducible gene 1 -- SARM sterile-α and TIR motif containing protein; Higher-order assembly signaling -- Inflammasome -- Nucleotide binding and oligomerization domain, leucine-rich repeat-containing/nucleotide and oligomerization domain-like receptor (NLR) -- RIG-I-like receptor (RLR) -- Signaling by cooperative assembly formation (SCAF) -- Toll-like receptor (TLR); Cytology -- Periodicals; Developmental biology -- Periodicals; 571.6
• DOI: 10.1016/j.semcdb.2018.05.002
• Languages: English
• ISSNs: 1084-9521

Abstract

Highlights: Signaling by cooperative assembly formation (SCAF) is ubiquitous in innate immunity pathways, including inflammasome and Toll-like receptor pathways. SCAF can be regulated by proteins that mimic the signaling components; they can be produced by mammalian cells and pathogens. The mechanisms of SCAF regulation by protein mimics may include capping or incorporating into filamentous assemblies. Abstract: Innate immunity pathways constitute the first line of defense against infections and cellular damage. An emerging concept in these pathways is that signaling involves the formation of finite ( e.g. rings in NLRs) or open-ended higher-order assemblies ( e.g. filamentous assemblies by members of the death-fold family and TIR domains). This signaling by cooperative assembly formation (SCAF) mechanism allows rapid and strongly amplified responses to minute amounts of stimulus. While the characterization of the molecular mechanisms of SCAF has seen rapid progress, little is known about its regulation. One emerging theme involves proteins produced both in host cells and by pathogens that appear to mimic the signaling components. Recently characterized examples involve the capping of the filamentous assemblies formed by caspase-1 CARDs by the CARD-only protein INCA, and those formed by caspase-8 by the DED-containing protein MC159. By contrast, the CARD-only protein ICEBERG and the DED-containing protein cFLIP incorporate into signaling filaments and presumably interfere with proximity based activation of caspases. We review selected examples of SCAF in innate immunity pathways and focus on the current knowledge on signaling component mimics produced by mammalian and pathogen cells and what is known about their mechanisms of action.