Zhenhang Chen
Chen Shen
Tian-Min Fu
1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA;
2 Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA;
3 The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
Funds: T.M.F. is supported by the Ohio State University Startup fund and C. S. is supported by a Cancer Research Institute Irvington Postdoctoral Fellowship. We apologize for incomplete citations due to space limitations.
Received Date: 2020-12-03
Accepted Date:2021-03-01
Abstract
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 higherorder assemblies:1) ordered, solid-like large supramolecular complexes formed by stable and rigid protein-protein interactions, and 2) liquid-like phaseseparated 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: higher-order assembly,
phase separation,
signalosome,
cGAS,
inflammasome,
TCR,
BCR,
TLR,
RLR,
TNFR,
death domain,
immune signaling
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