[English] 日本語
Yorodumi
- PDB-8r8v: Human PADI4 in complex with cyclic peptide PADI4_11 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8r8v
TitleHuman PADI4 in complex with cyclic peptide PADI4_11
Components
  • Cyclic Peptide PADI4_11
  • Protein-arginine deiminase type-4
KeywordsCYTOSOLIC PROTEIN / PADI4 / peptidyl arginine deiminase / Cyclic Peptide
Function / homology
Function and homology information


histone arginine deiminase activity / protein-arginine deiminase / histone H3R2 arginine deiminase activity / histone H3R8 arginine deiminase activity / histone H3R17 arginine deiminase activity / histone H3R26 arginine deiminase activity / histone H4R3 arginine deiminase activity / histone H1R54 arginine deiminase activity / histone H2AR3 arginine deiminase activity / protein-arginine deiminase activity ...histone arginine deiminase activity / protein-arginine deiminase / histone H3R2 arginine deiminase activity / histone H3R8 arginine deiminase activity / histone H3R17 arginine deiminase activity / histone H3R26 arginine deiminase activity / histone H4R3 arginine deiminase activity / histone H1R54 arginine deiminase activity / histone H2AR3 arginine deiminase activity / protein-arginine deiminase activity / stem cell population maintenance / Chromatin modifying enzymes / post-translational protein modification / protein modification process / nucleosome assembly / chromatin organization / chromatin remodeling / innate immune response / calcium ion binding / protein-containing complex / nucleoplasm / identical protein binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Protein-arginine deiminase / Protein-arginine deiminase, C-terminal / Protein-arginine deiminase (PAD), N-terminal / Protein-arginine deiminase (PAD), central domain / Protein-arginine deiminase, central domain superfamily / PAD, N-terminal domain superfamily / Protein-arginine deiminase (PAD) / Protein-arginine deiminase (PAD) N-terminal domain / Protein-arginine deiminase (PAD) middle domain / Cupredoxin
Similarity search - Domain/homology
Protein-arginine deiminase type-4
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsBenton, D.J. / Bertran, M.T. / Walport, L.J.
Funding support United Kingdom, 3items
OrganizationGrant numberCountry
The Francis Crick InstituteCC2030 United Kingdom
The Francis Crick InstituteFC0010129 United Kingdom
The Francis Crick InstituteFC001134 United Kingdom
CitationJournal: Nat Commun / Year: 2024
Title: A cyclic peptide toolkit reveals mechanistic principles of peptidylarginine deiminase IV regulation.
Authors: M Teresa Bertran / Robert Walmsley / Thomas Cummings / Iker Valle Aramburu / Donald J Benton / Rocio Mora Molina / Jayalini Assalaarachchi / Maria Chasampalioti / Tessa Swanton / Dhira Joshi ...Authors: M Teresa Bertran / Robert Walmsley / Thomas Cummings / Iker Valle Aramburu / Donald J Benton / Rocio Mora Molina / Jayalini Assalaarachchi / Maria Chasampalioti / Tessa Swanton / Dhira Joshi / Stefania Federico / Hanneke Okkenhaug / Lu Yu / David Oxley / Simon Walker / Venizelos Papayannopoulos / Hiroaki Suga / Maria A Christophorou / Louise J Walport /
Abstract: Peptidylarginine deiminase IV (PADI4, PAD4) deregulation promotes the development of autoimmunity, cancer, atherosclerosis and age-related tissue fibrosis. PADI4 additionally mediates immune ...Peptidylarginine deiminase IV (PADI4, PAD4) deregulation promotes the development of autoimmunity, cancer, atherosclerosis and age-related tissue fibrosis. PADI4 additionally mediates immune responses and cellular reprogramming, although the full extent of its physiological roles is unexplored. Despite detailed molecular knowledge of PADI4 activation in vitro, we lack understanding of its regulation within cells, largely due to a lack of appropriate systems and tools. Here, we develop and apply a set of potent and selective PADI4 modulators. Using the mRNA-display-based RaPID system, we screen >10 cyclic peptides for high-affinity, conformation-selective binders. We report PADI4_3, a cell-active inhibitor specific for the active conformation of PADI4; PADI4_7, an inert binder, which we functionalise for the isolation and study of cellular PADI4; and PADI4_11, a cell-active PADI4 activator. Structural studies with PADI4_11 reveal an allosteric binding mode that may reflect the mechanism that promotes cellular PADI4 activation. This work contributes to our understanding of PADI4 regulation and provides a toolkit for the study and modulation of PADI4 across (patho)physiological contexts.
History
DepositionNov 30, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 27, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Protein-arginine deiminase type-4
C: Cyclic Peptide PADI4_11
D: Cyclic Peptide PADI4_11
B: Protein-arginine deiminase type-4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)153,12414
Polymers152,7234
Non-polymers40110
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area8650 Å2
ΔGint-135 kcal/mol
Surface area53900 Å2
MethodPISA

-
Components

#1: Protein Protein-arginine deiminase type-4


Mass: 74803.719 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PADI4 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9UM07
#2: Protein/peptide Cyclic Peptide PADI4_11


Mass: 1557.797 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)
#3: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: Ca
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Human PADI4 in complex with cyclic peptide PADI4_11 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.15 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationInstrument: FEI VITROBOT MARK III / Cryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 28 e/Å2 / Film or detector model: TFS FALCON 4i (4k x 4k)
EM imaging opticsEnergyfilter name: TFS Selectris / Energyfilter slit width: 10 eV

-
Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C2 (2 fold cyclic)
3D reconstructionResolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 79000 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00310452
ELECTRON MICROSCOPYf_angle_d0.57314184
ELECTRON MICROSCOPYf_dihedral_angle_d4.4071370
ELECTRON MICROSCOPYf_chiral_restr0.0461582
ELECTRON MICROSCOPYf_plane_restr0.0051836

+
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