Death domain fold proteins in immune signaling and transcriptional regulation

Death domain fold (DDF) superfamily comprises of the death domain (DD), death effector domain (DED), caspase activation recruitment domain (CARD), and pyrin domain (PYD). By utilizing a conserved mode of interaction involving six distinct surfaces, a DDF serves as a building block that can densely p...

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Bibliographic Details
Published in:The FEBS journal 2022-07, Vol.289 (14), p.4082-4097
Main Authors: Huoh, Yu‐San, Hur, Sun
Format: Article
Language:English
Subjects:
Annotations
Assembly
Biological activity
Biological Phenomena
CARD Signaling Adaptor Proteins - metabolism
Caspase
Cytoskeletal Proteins - chemistry
Death
Death Domain
death domain fold
filament assembly
Filaments
Gene regulation
high‐order protein oligomerization
immune signaling
Inflammasomes
Liquid phases
Mortality
Oligomerization
Phase separation
Proteins
Pyrin protein
Signal processing
Signal Transduction
Signaling
Sp100 family
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Description
Summary:Death domain fold (DDF) superfamily comprises of the death domain (DD), death effector domain (DED), caspase activation recruitment domain (CARD), and pyrin domain (PYD). By utilizing a conserved mode of interaction involving six distinct surfaces, a DDF serves as a building block that can densely pack into homomultimers or filaments. Studies of immune signaling components have revealed that DDF‐mediated filament formation plays a central role in mediating signal transduction and amplification. The unique ability of DDFs to self‐oligomerize upon external signals and induce oligomerization of partner molecules underlies key processes in many innate immune signaling pathways, as exemplified by RIG‐I‐like receptor signalosome and inflammasome assembly. Recent studies showed that DDFs are not only limited to immune signaling pathways, but also are involved with transcriptional regulation and other biological processes. Considering that DDF annotation still remains a challenge, the current list of DDFs and their functions may represent just the tip of the iceberg within the full spectrum of DDF biology. In this review, we discuss recent advances in our understanding of DDF functions, structures, and assembly architectures with a focus on CARD‐ and PYD‐containing proteins. We also discuss areas of future research and the potential relationship of DDFs with biomolecular condensates formed by liquid–liquid phase separation (LLPS). The death domain fold (DDF) is a protein interaction motif that has the unique ability to densely pack into homomultimers or filaments. DDF‐mediated filament formation plays a central role in mediating immune signaling pathways and transcriptional regulation. In this review, we discuss recent advances in our understanding of DDF functions, structures, and assembly architectures. We also consider areas of future research and the potential relationship of DDFs with biomolecular condensates. ​
ISSN:1742-464X
1742-4658
DOI:10.1111/febs.15901