Evidence map›Paper›PMID 38733997›Full record

ArticleImmunity2024

Structural transitions enable interleukin-18 maturation and signaling.

Ying Dong, Jeffrey P Bonin, Pascal Devant, Zhuoyi Liang, Alexander I M Sever, Julian Mintseris, James M Aramini, Gang Du, Stephen P Gygi, Jonathan C Kagan and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
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

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Making invisible excited-state structures of pro-interleukin-18 visible by combining NMR and machine learning.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. The Roles of Interleukin-18 in Inflammation and Autoimmune Disease.Clinical reviews in allergy & immunology · 2026
    Review
  6. IL-18-Mediated Tumor Immune Evasion.Current issues in molecular biology · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. IL-18 and IL-18BP: A Unique Dyad in Health and Disease.International journal of molecular sciences · 2024
    Review
  15. Article
  16. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Ying DongDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Jeffrey P BoninDepartments of Molecular Genetics and Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada.
Pascal DevantDivision of Gastroenterology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Zhuoyi LiangBioscience and Biomedical Engineering Thrust, Brain and Intelligence Research Institute, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, China.
Alexander I M SeverDepartment of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada.
Julian MintserisDepartment of Cell Biology, Harvard Medical School, Harvard University, Boston, MA, USA.
James M AraminiDepartments of Molecular Genetics and Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada.
Gang DuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Stephen P GygiDepartment of Cell Biology, Harvard Medical School, Harvard University, Boston, MA, USA.
Jonathan C KaganDivision of Gastroenterology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: jonathan.kagan@childrens.harvard.edu.
Lewis E KayDepartments of Molecular Genetics and Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada. Electronic address: lewis.kay@utoronto.ca.
Hao WuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. Electronic address: wu@crystal.harvard.edu.

Funding

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
STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
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
Regulation of immunity by the cGAS-STING pathwayR01AI167993 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI JONATHAN C KAGAN · 2022 to 2026
$3.9M
Elucidating the functional mechanism of NLRP3 inflammasome activationR01AI177778 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI Hao Wu · 2023 to 2026
$2.8M
Characterization of the myddosome, a protein complex that controls TLR signalingR01AI116550 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI KAGAN, JONATHAN C · 2017 to 2020
$1.8M
NIAID NIH HHS R01 AI116550NIAID NIH HHS R01 AI124491NIAID NIH HHS R01 AI167993NIAID NIH HHS R01 AI177778NICHD NIH HHS DP1 HD087988NIDDK NIH HHS P30 DK034854NIGMS NIH HHS U24 GM129547
6 · The paper itself

Abstract

Several interleukin-1 (IL-1) family members, including IL-1β and IL-18, require processing by inflammasome-associated caspases to unleash their activities. Here, we unveil, by cryoelectron microscopy (cryo-EM), two major conformations of the complex between caspase-1 and pro-IL-18. One conformation is similar to the complex of caspase-4 and pro-IL-18, with interactions at both the active site and an exosite (closed conformation), and the other only contains interactions at the active site (open conformation). Thus, pro-IL-18 recruitment and processing by caspase-1 is less dependent on the exosite than the active site, unlike caspase-4. Structure determination by nuclear magnetic resonance uncovers a compact fold of apo pro-IL-18, which is similar to caspase-1-bound pro-IL-18 but distinct from cleaved IL-18. Binding sites for IL-18 receptor and IL-18 binding protein are only formed upon conformational changes after pro-IL-18 cleavage. These studies show how pro-IL-18 is selected as a caspase-1 substrate, and why cleavage is necessary for its inflammatory activity.

Indexed as

Caspase 1Cryoelectron MicroscopyInterleukin-18Signal TransductionAnimalsBinding SitesHumansInflammasomesIntercellular Signaling Peptides and ProteinsMiceModels, MolecularProtein BindingProtein ConformationReceptors, Interleukin-18Caspase 1InflammasomesIntercellular Signaling Peptides and ProteinsInterleukin-18interleukin-18 binding proteinReceptors, Interleukin-18caspase-1conformational changecryo-EMcytokine cleavageIL-18inflammatory activityNMRpro-IL-18

Identifiers

PMID38733997
PMCPMC11236505

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.