Functional and structural characterization of zebrafish <scp>ASC</scp>

Li, Yajuan; Huang, Yi; Cao, Xiaocong; Yin, Xueying; Jin, Xuesong; Liu, Sheng; Jiang, Jiansheng; Jiang, Wei; Xiao, Tsan Sam; Zhou, Rongbin; Wang, Xuejuan; Hu, Bing; Jin, Tengchuan

doi:10.1111/febs.14514

Cited by 28 publications

(16 citation statements)

References 52 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The crystallographic structure of human ASC CARD is composed of six amphipathic α-helices engaging a hydrophobic core, similar to what has been found for other CARD domains 25,33,34 . The structure was refined to 2.0 Å resolution and exhibits excellent agreement with the cryo-EM structure of ASC CARD in filaments with an root mean squared deviation (RMSD) of 0.502 Å 31 (Fig.…”

Section: The Structure Of the Asc Card Is Highly Conservedsupporting

confidence: 66%

Homotypic CARD-CARD interaction is critical for the activation of NLRP1 inflammasome

Zhou

Liu

et al. 2021

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Cytosolic inflammasomes are supramolecular complexes that are formed in response to intracellular pathogens and danger signals. However, as to date, the detailed description of a homotypic caspase recruitment domain (CARD) interaction between NLRP1 and ASC has not been presented. We found the CARD–CARD interaction between purified NLRP1CARD and ASCCARD experimentally and the filamentous supramolecular complex formation in an in vitro proteins solution. Moreover, we determined a high-resolution crystal structure of the death domain fold of the human ASCCARD. Mutational and structural analysis revealed three conserved interfaces of the death domain superfamily (Type I, II, and III), which mediate the assembly of the NLRP1CARD/ASCCARD complex. In addition, we validated the role of the three major interfaces of CARDs in assembly and activation of NLRP1 inflammasome in vitro. Our findings suggest a Mosaic model of homotypic CARD interactions for the activation of NLRP1 inflammasome. The Mosaic model provides insights into the mechanisms of inflammasome assembly and signal transduction amplification.

show abstract

Section: The Structure Of the Asc Card Is Highly Conservedsupporting

confidence: 66%

Homotypic CARD-CARD interaction is critical for the activation of NLRP1 inflammasome

Zhou

Liu

et al. 2021

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nlrp6 is able to form inflammasome complexes in response to Edwarsiella piscicida in vivo, confirming its function as inflammasome sensor [56]. Another predicted protein, referred to as Nlp3 isoform X1, is able to interact with zebrafish Asc in vitro via the interaction of their PYD domains [57]. However, the downstream caspase recruitment and activation dynamics differ to the ones in the mammalian NLRP inflammasomes.…”

Section: Evolutionary Conservation Of Inflammasome Components In Zmentioning

confidence: 99%

“…Upon recruitment, ASC self-assembles into large signalling platforms, named ASC specks or foci, which are considered a hallmark of canonical inflammasome activation [64,65]. Unlike in mammals, zebrafish Asc PYD domain is critical for both auto-assembly and downstream proinflammatory caspase recruitment via PYD-PYD interactions [27,57]. Despite this difference, zebrafish Asc functionality seems to be conserved between zebrafish and mammals, as pyroptosis of zebrafish keratinocytes and macrophages has been recently visualized after Asc speck formation in vivo [27,29].…”

Section: Evolutionary Conservation Of Inflammasome Components In Zmentioning

confidence: 99%

“…This assumption was originally backed by percentage of protein sequence homology and protease substrate preference [41]. Further functional analysis reported that only the Caspa PYD domain, but not the one of Caspb, is able to directly interact with Asc [27,41,57], and therefore promote Asc-dependent pyroptosis [27]. On the other hand, the Caspb PYD prodomain, but not the one in Caspa, is able to bind to LPS when overexpressed in HEK293T cells [42].…”

Section: Evolutionary Conservation Of Inflammasome Components In Zmentioning

confidence: 99%

“…While the abilities of Caspa and Caspb to cleave Gasdermin remains to be studied, they are both able to cleave Il1b, albeit with different specificities [52]. Interestingly, Caspa and Caspb can directly interact in vitro via its PYD domains, thus opening the possibility of Caspa/Caspb oligomerization needed to fully mature Il1b [57]. In contrast, mammalian CASP4/5/11 cleave Gasdermin D but not proinflammatory cytokines during pyroptosis [67].…”

Section: Evolutionary Conservation Of Inflammasome Components In Zmentioning

confidence: 99%

See 2 more Smart Citations

Zebrafish in Inflammasome Research

Forn-Cuní

Meijer

Varela

2019

Cells

View full text Add to dashboard Cite

Inflammasomes are cytosolic multiprotein complexes that regulate inflammatory responses to danger stimuli and infection, and their dysregulation is associated with an increasing number of autoinflammatory diseases. In recent years, zebrafish models of human pathologies to study inflammasome function in vivo have started to emerge. Here, we discuss inflammasome research in zebrafish in light of current knowledge about mammalian inflammasomes. We summarize the evolutionary conservation of inflammasome components between zebrafish and mammals, highlighting the similarities and possible divergence in functions of these components. We present new insights into the evolution of the caspase-1 family in the teleost lineage, and how its evolutionary origin may help contextualize its functions. We also review existing infectious and non-infectious models in zebrafish in which inflammasomes have been directly implicated. Finally, we discuss the advantages of zebrafish larvae for intravital imaging of inflammasome activation and summarize available tools that will help to advance inflammasome research.

show abstract