Death domain fold proteins in immune signaling and transcriptional regulation.
Death domain fold proteins in immune signaling and transcriptional regulation.
复制标题
免疫信号传导和转录调节中的死亡结构域折叠蛋白。
DOI：
10.1111/febs.15901
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发表时间：
2022-07
期刊：
影响因子：
--
通讯作者：
Hur S
中科院分区：
文献类型：
--
作者：
Huoh YS;Hur S
死亡结构域折叠（DDF）超家族由死亡结构域（DD）、死亡效应结构域（DED）、半胱天冬酶激活募集结构域（CARD）和pyrin结构域（PYD）组成。通过利用涉及六个不同表面的保守相互作用模式，DDF充当可以密集地包装成同源多聚体或细丝的构建块。免疫信号成分的研究表明，DDF介导的细丝形成在介导信号转导和放大中起着核心作用。DDF在外部信号下自我寡聚化并诱导伴侣分子寡聚化的独特能力是许多先天免疫信号传导途径中的关键过程的基础，如RIG-I样受体信号体和炎性体组装所例示。近年来的研究表明DDFs不仅参与免疫信号传导，还参与转录调控和其他生物学过程。考虑到DDF注释仍然是一个挑战，DDF及其功能的当前列表可能只是DDF生物学全谱中的冰山一角。在这篇综述中，我们讨论了最近的进展，我们的理解DDF的功能，结构和组装架构的重点是CARD和PYD蛋白。我们还讨论了未来的研究领域和潜在的DDFs与生物分子凝聚物形成的液-液相分离（LLPS）的关系。
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 homo-multimers 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 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).
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