Structural characterization of TIR-domain signalosomes through a combination of structural biology approaches

Akansha Bhatt, Biswa P. Mishra, Weixi Gu, Mitchell Sorbello, Hongyi Xu, Thomas Ve*, Bostjan Kobe*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)

Abstract

The TIR (Toll/interleukin-1 receptor) domain represents a vital structural element shared by proteins with roles in immunity signalling pathways across phyla (from humans and plants to bacteria). Decades of research have finally led to identifying the key features of the molecular basis of signalling by these domains, including the formation of open-ended (filamentous) assemblies (responsible for the signalling by cooperative assembly formation mechanism, SCAF) and enzymatic activities involving the cleavage of nucleotides. We present a historical perspective of the research that led to this understanding, highlighting the roles that different structural methods played in this process: X-ray crystallography (including serial crystallography), microED (microcrystal electron diffraction), NMR (nuclear magnetic resonance) spectroscopy and cryo-EM (cryogenic electron microscopy) involving helical reconstruction and single-particle analysis. This perspective emphasizes the complementarity of different structural approaches.

Original languageEnglish
Pages (from-to)695-707
Number of pages13
JournalIUCrJ
Volume11
Issue numberPt 5
DOIs
Publication statusPublished - Sept 2024
Externally publishedYes

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