[English] 日本語
Yorodumi
- EMDB-21160: Gasdermin D pore -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-21160
TitleGasdermin D pore
Map dataPore-forming protein Gasdermin-D
Sample
  • Complex: Pore-forming protein Gasdermin-D
    • Protein or peptide: Gasdermin-D, N-terminal
KeywordsPore-forming protein / LIPID BINDING PROTEIN
Function / homology
Function and homology information


pyroptotic cell death / Release of apoptotic factors from the mitochondria / pore complex assembly / NLRP3 inflammasome complex / wide pore channel activity / Regulation of TLR by endogenous ligand / phosphatidic acid binding / Interleukin-1 processing / cardiolipin binding / phosphatidylinositol-4-phosphate binding ...pyroptotic cell death / Release of apoptotic factors from the mitochondria / pore complex assembly / NLRP3 inflammasome complex / wide pore channel activity / Regulation of TLR by endogenous ligand / phosphatidic acid binding / Interleukin-1 processing / cardiolipin binding / phosphatidylinositol-4-phosphate binding / pyroptotic inflammatory response / phosphatidylserine binding / Pyroptosis / protein secretion / Purinergic signaling in leishmaniasis infection / phosphatidylinositol-4,5-bisphosphate binding / positive regulation of interleukin-1 beta production / mitochondrial membrane / protein homooligomerization / positive regulation of inflammatory response / specific granule lumen / tertiary granule lumen / defense response to Gram-negative bacterium / ficolin-1-rich granule lumen / defense response to Gram-positive bacterium / defense response to bacterium / innate immune response / Neutrophil degranulation / extracellular space / extracellular region / nucleoplasm / membrane / plasma membrane / cytosol
Similarity search - Function
Gasdermin, PUB domain / Gasdermin PUB domain / Gasdermin, pore forming domain / Gasdermin pore forming domain
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.9 Å
AuthorsXia S / Ruan J
Funding support United States, 3 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01AI139914 United States
National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD)DP1HD087988 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01AI124491 United States
CitationJournal: Nature / Year: 2021
Title: Gasdermin D pore structure reveals preferential release of mature interleukin-1.
Authors: Shiyu Xia / Zhibin Zhang / Venkat Giri Magupalli / Juan Lorenzo Pablo / Ying Dong / Setu M Vora / Longfei Wang / Tian-Min Fu / Matthew P Jacobson / Anna Greka / Judy Lieberman / Jianbin Ruan / Hao Wu /
Abstract: As organelles of the innate immune system, inflammasomes activate caspase-1 and other inflammatory caspases that cleave gasdermin D (GSDMD). Caspase-1 also cleaves inactive precursors of the ...As organelles of the innate immune system, inflammasomes activate caspase-1 and other inflammatory caspases that cleave gasdermin D (GSDMD). Caspase-1 also cleaves inactive precursors of the interleukin (IL)-1 family to generate mature cytokines such as IL-1β and IL-18. Cleaved GSDMD forms transmembrane pores to enable the release of IL-1 and to drive cell lysis through pyroptosis. Here we report cryo-electron microscopy structures of the pore and the prepore of GSDMD. These structures reveal the different conformations of the two states, as well as extensive membrane-binding elements including a hydrophobic anchor and three positively charged patches. The GSDMD pore conduit is predominantly negatively charged. By contrast, IL-1 precursors have an acidic domain that is proteolytically removed by caspase-1. When permeabilized by GSDMD pores, unlysed liposomes release positively charged and neutral cargoes faster than negatively charged cargoes of similar sizes, and the pores favour the passage of IL-1β and IL-18 over that of their precursors. Consistent with these findings, living-but not pyroptotic-macrophages preferentially release mature IL-1β upon perforation by GSDMD. Mutation of the acidic residues of GSDMD compromises this preference, hindering intracellular retention of the precursor and secretion of the mature cytokine. The GSDMD pore therefore mediates IL-1 release by electrostatic filtering, which suggests the importance of charge in addition to size in the transport of cargoes across this large channel.
History
DepositionJan 3, 2020-
Header (metadata) releaseApr 21, 2021-
Map releaseApr 21, 2021-
UpdateMay 29, 2024-
Current statusMay 29, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.013
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.013
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6vfe
  • Surface level: 0.018
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6vfe
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_21160.png

Downloads & links

-
Map

FileDownload / File: emd_21160.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationPore-forming protein Gasdermin-D
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.7 Å/pix.
x 240 pix.
= 408. Å		1.7 Å/pix.
x 240 pix.
= 408. Å		1.7 Å/pix.
x 240 pix.
= 408. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.7 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.013 / Movie #1: 0.013
Minimum - Maximum-0.055482913 - 0.11992676
Average (Standard dev.)0.00044610424 (±0.0040871436)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions240240240
Spacing240240240
CellA=B=C: 408.0 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.71.71.7
M x/y/z240240240
origin x/y/z0.0000.0000.000
length x/y/z408.000408.000408.000
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS240240240
D min/max/mean-0.0550.1200.000

-
Supplemental data

-
Sample components

-
Entire : Pore-forming protein Gasdermin-D

EntireName: Pore-forming protein Gasdermin-D
Components
  • Complex: Pore-forming protein Gasdermin-D
    • Protein or peptide: Gasdermin-D, N-terminal

-
Supramolecule #1: Pore-forming protein Gasdermin-D

SupramoleculeName: Pore-forming protein Gasdermin-D / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 1 MDa

-
Macromolecule #1: Gasdermin-D, N-terminal

MacromoleculeName: Gasdermin-D, N-terminal / type: protein_or_peptide / ID: 1 / Number of copies: 33 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 26.850221 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MGSAFERVVR RVVQELDHGG EFIPVTSLQS STGFQPYCLV VRKPSSSWFW KPRYKCVNLS IKDILEPDAA EPDVQRGRSF HFYDAMDGQ IQGSVELAAP GQAKIAGGAA VSDSSSTSMN VYSLSVDPNT WQTLLHERHL RQPEHKVLQQ LRSRGDNVYV V TEVLQTQK ...String:
MGSAFERVVR RVVQELDHGG EFIPVTSLQS STGFQPYCLV VRKPSSSWFW KPRYKCVNLS IKDILEPDAA EPDVQRGRSF HFYDAMDGQ IQGSVELAAP GQAKIAGGAA VSDSSSTSMN VYSLSVDPNT WQTLLHERHL RQPEHKVLQQ LRSRGDNVYV V TEVLQTQK EVEVTRTHKR EGSGRFSLPG ATCEQGEGQG HLSQKKTVTI PSGSTLAFRV AQLVIDSDLD VLLFPDKKQR TF Q

UniProtKB: Gasdermin-D

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 63.25 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: PDB ENTRY
Final reconstructionApplied symmetry - Point group: C33 (33 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 90222
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
FSC plot (resolution estimation)

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more