Abstract
Signaling pathways in innate and adaptive immunity play vital roles in pathogen recognition and the functions of immune cells. Higher-order assemblies have recently emerged as a central principle that governs immune signaling and, by extension, cellular communication in general. There are mainly two types of higher-order assemblies: 1) ordered, solid-like large supramolecular complexes formed by stable and rigid protein-protein interactions, and 2) liquid-like phase-separated condensates formed by weaker and more dynamic intermolecular interactions. This review covers key examples of both types of higher-order assemblies in major immune pathways. By placing emphasis on the molecular structures of the examples provided, we discuss how their structural organization enables elegant mechanisms of signaling regulation.
Keywords:
BCR; RLR; TCR; TLR; TNFR; cGAS; death domain; higher-order assembly, phase separation, signalosome; immune signaling; inflammasome.
© 2021. The Author(s).
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adaptive Immunity
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Animals
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DEAD Box Protein 58 / genetics
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DEAD Box Protein 58 / immunology
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DEAD Box Protein 58 / metabolism
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / immunology
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DEAD-box RNA Helicases / metabolism
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Gene Expression Regulation
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Humans
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Immunity, Innate*
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Inflammasomes / genetics
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Inflammasomes / immunology*
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Inflammasomes / ultrastructure
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Models, Molecular
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Multiprotein Complexes / genetics
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Multiprotein Complexes / immunology*
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Multiprotein Complexes / metabolism
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Protein Conformation
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Protein Interaction Mapping
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Receptors, Antigen, B-Cell / genetics
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Receptors, Antigen, B-Cell / immunology*
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Receptors, Antigen, B-Cell / metabolism
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology*
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism
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Receptors, Tumor Necrosis Factor, Type I / genetics
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Receptors, Tumor Necrosis Factor, Type I / immunology
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Receptors, Tumor Necrosis Factor, Type I / metabolism
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Signal Transduction / immunology*
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Toll-Like Receptors / genetics
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Toll-Like Receptors / immunology
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Toll-Like Receptors / metabolism
Substances
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Inflammasomes
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Multiprotein Complexes
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Receptors, Antigen, B-Cell
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Receptors, Antigen, T-Cell
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Receptors, Immunologic
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Receptors, Tumor Necrosis Factor, Type I
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TNFRSF1A protein, human
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Toll-Like Receptors
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RIGI protein, human
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DEAD Box Protein 58
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DEAD-box RNA Helicases