Evidence map›Paper›PMID 35115408›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Electrostatic influence on IL-1 transport through the GSDMD pore.

Wen Jun Xie, Shiyu Xia, Arieh Warshel, Hao Wu

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

24 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. [HeZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025
    Article
  8. Review
  9. Article
  10. Mechanistic insights from inflammasome structures.Nature reviews. Immunology · 2024
    Review
  11. Article
  12. The gasdermin family: emerging therapeutic targets in diseases.Signal transduction and targeted therapy · 2024
    Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Review
  20. Gasdermins in sepsis.Frontiers in immunology · 2023
    Review
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

4 authors at 3 institutions in 1 country.

Wen Jun XieDepartment of Chemistry, University of Southern California, Los Angeles, CA 90089.
Shiyu XiaDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Arieh WarshelDepartment of Chemistry, University of Southern California, Los Angeles, CA 90089; warshel@usc.edu wu@crystal.harvard.edu.
Hao WuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115; warshel@usc.edu wu@crystal.harvard.edu.
University of Southern California · USBoston Children's Hospital · USHarvard University · US

Funding

Multiscale Simulations of Biological Systems and ProcessesR35GM122472 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ARIEH WARSHEL · 2017 to 2026
$5.0M
THEORETICAL STUDIES OF ENZYMATIC REACTIONSR01GM024492 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI WARSHEL, ARIEH · 1985 to 2017
$5.0M
Elucidating the structural mechanism of pore formation by the (GSDM) Gasdermin familyR01AI139914 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI WU, HAO · 2018 to 2022
$2.6M
NIAID NIH HHS R01 AI139914NIGMS NIH HHS R01 GM024492NIGMS NIH HHS R35 GM122472
6 · The paper itself

Abstract

A variety of signals, including inflammasome activation, trigger the formation of large transmembrane pores by gasdermin D (GSDMD). There are primarily two functions of the GSDMD pore, to drive lytic cell death, known as pyroptosis, and to permit the release of leaderless interleukin-1 (IL-1) family cytokines, a process that does not require pyroptosis. We are interested in the mechanism by which the GSDMD pore channels IL-1 release from living cells. Recent studies revealed that electrostatic interaction, in addition to cargo size, plays a critical role in GSDMD-dependent protein release. Here, we determined computationally that to enable electrostatic filtering against pro-IL-1β, acidic lipids in the membrane need to effectively neutralize positive charges in the membrane-facing patches of the GSDMD pore. In addition, we predicted that salt has an attenuating effect on electrostatic filtering and then validated this prediction using a liposome leakage assay. A calibrated electrostatic screening factor is necessary to account for the experimental observations, suggesting that ion distribution within the pore may be different from the bulk solution. Our findings corroborate the electrostatic influence of IL-1 transport exerted by the GSDMD pore and reveal extrinsic factors, including lipid and salt, that affect the electrostatic environment.

Indexed as

AnimalsCell MembraneGasderminsHumansInflammasomesInterleukin-1MicePhosphate-Binding ProteinsPore Forming Cytotoxic ProteinsPyroptosisStatic ElectricityGasderminsGSDMD protein, humanInflammasomesInterleukin-1Phosphate-Binding ProteinsPore Forming Cytotoxic Proteinschannelelectrostaticsgasdermin Dinflammasomeinterleukin-1

Identifiers

PMID35115408
PMCPMC8833203
OpenAlexW4210784717

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.