Higher-order assemblies in immune signaling: supramolecular complexes and phase separation

Shiyu Xia, Zhenhang Chen, Chen Shen, Tian Min Fu

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations


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.

Original languageEnglish
Pages (from-to)680-694
Number of pages15
JournalProtein and Cell
Issue number9
StatePublished - Sep 2021


  • BCR
  • RLR
  • TCR
  • TLR
  • TNFR
  • cGAS
  • death domain
  • higher-order assembly, phase separation, signalosome
  • immune signaling
  • inflammasome


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