Evidence map›Paper›PMID 39854601›Full record

ArticlePLoS pathogens2025

Diverse autoinhibitory mechanisms of FIIND-containing proteins: Insight into regulation of NLRP1 and CARD8 inflammasome.

Jingfan Zhou, Chengrong Liu, Xin Wang, Zhenshan Liu, Zizhen Ming, Yonggang Wang, Chunxia Wang, Qiming Liang

Abstract read
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In one paragraph

Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Jingfan ZhouInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chengrong LiuInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xin WangInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhenshan LiuInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zizhen MingInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yonggang WangDepartment of Cardiovascular Center, The First Hospital of Jilin University, Changchun, China.
Chunxia WangInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qiming LiangInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0003-4792-1547

Funding

Innovative Research Team of High-level Local Universities in ShanghaiNational Key Research and Development Project of ChinaProgram of Shanghai Academic/Technology Research LeaderShanghai Frontiers Science Center of Cellular Homeostasis and Human DiseaseShanghai Science and Technology Commission
6 · The paper itself

Abstract

Function-to-find domain (FIIND)-containing proteins, including NLRP1 and CARD8, are vital components of the inflammasome signaling pathway, critical for the innate immune response. These proteins exist in various forms due to autoproteolysis within the FIIND domain, resulting in full-length (FL), cleaved N-terminal (NT), and cleaved C-terminal (CT) peptides, which form autoinhibitory complexes in the steady state. However, the detailed mechanism remains elusive. Here, we found that both NLRP1 paralogs and CARD8 form two conserved autoinhibitory complexes involving NT-CT interactions and FL-CT interactions, but with distinct mechanisms. Specifically, the Linker3 region located between LRR and FIIND in murine NLRP1b (mNLRP1b) plays an essential role in forming the NT-CT autoinhibitory complexes, while the ZU5 of rat NLRP1 (rNLRP1) and CARD8 mediates their NT-CT interaction. In addition, we explored the involvement of the cellular protease dipeptidyl peptidases 9 (DPP9) in these complexes, revealing differential interactions and the significance of domain structure. Besides the FL-DPP9-CT complex, DPP9 interacts with NTs of mNLRP1b, rNLRP1, and CARD8 through their ZU5 subdomains, forming NT-DPP9-CT complex; however, DPP9 cannot bind to NTs of hNLRP1. Further functional assay indicated that although DPP9 is involved in the NT-CT complex of rodent NLRP1 and CARD8, it does not influence the inhibitory activity of NT on CT. Our study enhanced the understanding of the regulatory functions of FIIND-containing proteins in inflammasome autoinhibition and activation and underscored the complexity of their interactions within the immune response.

Indexed as

Adaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsInflammasomesAnimalsHEK293 CellsHumansImmunity, InnateMiceNeoplasm ProteinsNLR ProteinsRatsSignal TransductionAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsCARD8 protein, humanCARD Signaling Adaptor ProteinsInflammasomesNALP1 protein, mouseNeoplasm ProteinsNLRP1 protein, humanNLR Proteins

Identifiers

PMID39854601
PMCPMC11760013

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.