Evidence map›Paper›PMID 33420033›Full record

ArticleNature communications2021

Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes.

L Robert Hollingsworth, Liron David, Yang Li, Andrew R Griswold, Jianbin Ruan, Humayun Sharif, Pietro Fontana, Elizabeth L Orth-He, Tian-Min Fu, Daniel A Bachovchin and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 81 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. NLRP1B is an integrated decoy that subvertsProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Article
  8. Supramolecular Assemblies Drive Activation of Inflammasomes.Advances in experimental medicine and biology · 2026
    Review
  9. Review
  10. Review
  11. Article
  12. Toward targeting of inflammasome signaling in venous thrombosis.Journal of thrombosis and haemostasis : JTH · 2025
    Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

L Robert Hollingsworth *Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-4130-3580
Liron David *Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Yang Li *Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Andrew R GriswoldWeill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY, USA.
Jianbin RuanDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Humayun SharifDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Pietro FontanaDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Elizabeth L Orth-HeTri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Tian-Min FuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-6281-1752
Daniel A BachovchinPharmacology Program, Weill Cornell Graduate School of Medical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0001-8210-1662
Hao WuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA. wu@crystal.harvard.edu.ORCID http://orcid.org/0000-0002-7281-8579
Boston Children's Hospital · USMemorial Sloan Kettering Cancer Center · USThe University of Texas Southwestern Medical Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Pacific Northwest Center for Cryo-EM - Screening supplementU24GM129547 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI EVANS, JAMES E, GOUAUX, JAMES E · 2018 to 2023
$54.8M
Weill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1M
J. NRSA Training CoreTL1TR002386 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Genevieve Giny Fouda Amou ou · 2017 to 2026
$5.8M
NLRP1 and CARD8 Inflammasomes: Assembly, Regulation and Stress SensingR01AI124491 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI WU, HAO · 2016 to 2025
$5.1M
SMOCs: Novel Signal Transduction Complexes as New Targets for Drug DiscoveryDP1HD087988 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI WU, HAO · 2015 to 2019
$4.4M
Characterizing the Mechanism of DPP8/9 Inhibitor-Induced PyroptosisR01AI137168 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI Daniel Bachovchin · 2018 to 2026
$4.3M
Tri-Institutional PhD Program in Chemical BiologyT32GM115327 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI TAN, DEREK S · 2015 to 2019
$741k
Characterizing the DPP8/9 Pyroptotic Checkpoint with Chemoproteomic Protease Substrate ProfilingF30CA243444 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI GRISWOLD, ANDREW · 2019 to 2022
$193k
NCATS NIH HHS TL1 TR002386NCI NIH HHS F30 CA243444NCI NIH HHS P30 CA008748NIAID NIH HHS R01 AI124491NIAID NIH HHS R01 AI137168NICHD NIH HHS DP1 HD087988NIGMS NIH HHS T32 GM007739NIGMS NIH HHS T32 GM115327NIGMS NIH HHS U24 GM129547
6 · The paper itself

Abstract

NLRP1 and CARD8 are related cytosolic sensors that upon activation form supramolecular signalling complexes known as canonical inflammasomes, resulting in caspase-1 activation, cytokine maturation and/or pyroptotic cell death. NLRP1 and CARD8 use their C-terminal (CT) fragments containing a caspase recruitment domain (CARD) and the UPA (conserved in UNC5, PIDD, and ankyrins) subdomain for self-oligomerization, which in turn form the platform to recruit the inflammasome adaptor ASC (apoptosis-associated speck-like protein containing a CARD) or caspase-1, respectively. Here, we report cryo-EM structures of NLRP1-CT and CARD8-CT assemblies, in which the respective CARDs form central helical filaments that are promoted by oligomerized, but flexibly linked, UPAs surrounding the filaments. Through biochemical and cellular approaches, we demonstrate that the UPA itself reduces the threshold needed for NLRP1-CT and CARD8-CT filament formation and signalling. Structural analyses provide insights on the mode of ASC recruitment by NLRP1-CT and the contrasting direct recruitment of caspase-1 by CARD8-CT. We also discover that subunits in the central NLRP1

Indexed as

Adaptor Proteins, Signal TransducingAnkyrinsApoptosisApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCaspase 1Caspase Activation and Recruitment DomainCryoelectron MicroscopyDeath Domain Receptor Signaling Adaptor ProteinsHEK293 CellsHumansInflammasomesModels, MolecularNeoplasm ProteinsNLR ProteinsProtein Interaction Domains and MotifsAdaptor Proteins, Signal TransducingAnkyrinsApoptosis Regulatory ProteinsCARD8 protein, humanCARD Signaling Adaptor ProteinsCaspase 1Death Domain Receptor Signaling Adaptor ProteinsInflammasomesNeoplasm ProteinsNLRP1 protein, humanNLR ProteinsPIDD1 protein, human

Identifiers

PMID33420033
PMCPMC7794386
OpenAlexW3119851465

What OpenQuestion holds

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Registered trials

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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.