[English] 日本語
Yorodumi
- PDB-8iz7: cryo-EM structure of sulindac-bound hMRP4 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8iz7
Titlecryo-EM structure of sulindac-bound hMRP4
ComponentsATP-binding cassette sub-family C member 4
KeywordsMEMBRANE PROTEIN / cryo-EM structure of sulindac-bound hMRP4
Function / homology
Function and homology information


15-hydroxyprostaglandin dehydrogenase (NAD+) activity / purine nucleotide transmembrane transporter activity / cAMP transport / guanine nucleotide transmembrane transporter activity / ABC-type bile acid transporter activity / platelet dense granule membrane / platelet degranulation / leukotriene transport / prostaglandin transport / urate transport ...15-hydroxyprostaglandin dehydrogenase (NAD+) activity / purine nucleotide transmembrane transporter activity / cAMP transport / guanine nucleotide transmembrane transporter activity / ABC-type bile acid transporter activity / platelet dense granule membrane / platelet degranulation / leukotriene transport / prostaglandin transport / urate transport / prostaglandin transmembrane transporter activity / ABC-type glutathione S-conjugate transporter activity / glutathione transmembrane transporter activity / ABC-type glutathione-S-conjugate transporter / urate transmembrane transporter activity / : / external side of apical plasma membrane / xenobiotic transmembrane transport / prostaglandin secretion / export across plasma membrane / Paracetamol ADME / ABC-type xenobiotic transporter / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / Azathioprine ADME / ABC-type xenobiotic transporter activity / bile acid and bile salt transport / efflux transmembrane transporter activity / xenobiotic transmembrane transporter activity / cilium assembly / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / transport across blood-brain barrier / xenobiotic metabolic process / ABC-family proteins mediated transport / transmembrane transport / Platelet degranulation / basolateral plasma membrane / apical plasma membrane / intracellular membrane-bounded organelle / nucleolus / Golgi apparatus / ATP hydrolysis activity / ATP binding / membrane / plasma membrane
Similarity search - Function
ATP-binding cassette sub-family C member 4 / : / : / ABC transporter transmembrane region / ABC transporter type 1, transmembrane domain / ABC transporter integral membrane type-1 fused domain profile. / ABC transporter type 1, transmembrane domain superfamily / ABC transporter-like, conserved site / ABC transporters family signature. / ABC transporter ...ATP-binding cassette sub-family C member 4 / : / : / ABC transporter transmembrane region / ABC transporter type 1, transmembrane domain / ABC transporter integral membrane type-1 fused domain profile. / ABC transporter type 1, transmembrane domain superfamily / ABC transporter-like, conserved site / ABC transporters family signature. / ABC transporter / ABC transporter-like, ATP-binding domain / ATP-binding cassette, ABC transporter-type domain profile. / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Chem-SUZ / ATP-binding cassette sub-family C member 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å
AuthorsLiu, Z.M. / Huang, Y.
Funding support China, 1items
OrganizationGrant numberCountry
National Science Foundation (NSF, China) China
CitationJournal: Commun Biol / Year: 2023
Title: Structural basis for substrate and inhibitor recognition of human multidrug transporter MRP4.
Authors: Ying Huang / Chenyang Xue / Liangdong Wang / Ruiqian Bu / Jianqiang Mu / Yong Wang / Zhongmin Liu /
Abstract: Human multidrug resistance protein 4 (hMRP4, also known as ABCC4), with a representative topology of the MRP subfamily, translocates various substrates across the membrane and contributes to the ...Human multidrug resistance protein 4 (hMRP4, also known as ABCC4), with a representative topology of the MRP subfamily, translocates various substrates across the membrane and contributes to the development of multidrug resistance. However, the underlying transport mechanism of hMRP4 remains unclear due to a lack of high-resolution structures. Here, we use cryogenic electron microscopy (cryo-EM) to resolve its near-atomic structures in the apo inward-open and the ATP-bound outward-open states. We also capture the PGE1 substrate-bound structure and, importantly, the inhibitor-bound structure of hMRP4 in complex with sulindac, revealing that substrate and inhibitor compete for the same hydrophobic binding pocket although with different binding modes. Moreover, our cryo-EM structures, together with molecular dynamics simulations and biochemical assay, shed light on the structural basis of the substrate transport and inhibition mechanism, with implications for the development of hMRP4-targeted drugs.
History
DepositionApr 6, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Apr 10, 2024Provider: repository / Type: Initial release
Revision 1.0Apr 10, 2024Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Apr 10, 2024Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Apr 10, 2024Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Apr 10, 2024Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Apr 10, 2024Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Apr 10, 2024Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Apr 10, 2024Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Apr 10, 2024Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Apr 10, 2024Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Oct 23, 2024Group: Data collection / Database references / Structure summary
Category: citation / citation_author ...citation / citation_author / em_admin / pdbx_entry_details
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update / _pdbx_entry_details.has_protein_modification
Revision 1.2Jul 23, 2025Group: Data collection / Category: em_admin / em_software / Item: _em_admin.last_update / _em_software.name
Revision 1.1Jul 23, 2025Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Data processing / Experimental summary / Data content type: EM metadata / EM metadata / Category: em_admin / em_software / Data content type: EM metadata / EM metadata / Item: _em_admin.last_update / _em_software.name

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: ATP-binding cassette sub-family C member 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)153,5282
Polymers153,1711
Non-polymers3561
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein ATP-binding cassette sub-family C member 4 / MRP/cMOAT-related ABC transporter / Multi-specific organic anion transporter B / MOAT-B / Multidrug ...MRP/cMOAT-related ABC transporter / Multi-specific organic anion transporter B / MOAT-B / Multidrug resistance-associated protein 4


Mass: 153171.359 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ABCC4, MOATB, MRP4 / Production host: Homo sapiens (human)
References: UniProt: O15439, Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate, ABC-type xenobiotic transporter, ABC-type ...References: UniProt: O15439, Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate, ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter
#2: Chemical ChemComp-SUZ / [(1Z)-5-fluoro-2-methyl-1-{4-[methylsulfinyl]benzylidene}-1H-inden-3-yl]acetic acid / SULINDAC


Mass: 356.411 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H17FO3S / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: sulindac-bound hMRP4 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen 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: 1800 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.16_3549: / Classification: refinement
EM softwareName: PHENIX / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 151694 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00110015
ELECTRON MICROSCOPYf_angle_d0.44513571
ELECTRON MICROSCOPYf_dihedral_angle_d2.835979
ELECTRON MICROSCOPYf_chiral_restr0.0381574
ELECTRON MICROSCOPYf_plane_restr0.0021687

+
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