[English] 日本語
Yorodumi
- EMDB-4281: Zosuquidar and UIC2 Fab complex of human-mouse chimeric ABCB1 (AB... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-4281
TitleZosuquidar and UIC2 Fab complex of human-mouse chimeric ABCB1 (ABCB1HM)
Map dataZosuquidar complex of ABCB1HM-X. Final post-processed map after partial detergent belt removal.
Sample
  • Complex: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zosuquidar
    • Complex: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zosuquidar
      • Protein or peptide: Human-mouse chimeric ABCB1 (ABCBHM)
    • Complex: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zosuquidar
      • Protein or peptide: UIC2 Antigen Binding Fragment Light chain
      • Protein or peptide: UIC2 Antigen Binding Fragment Heavy Chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: Zosuquidar
KeywordsMembrane Transport Protein ABCB1 ABC Exporter Small molecule inhibitor Antibody complex / MEMBRANE PROTEIN
Function / homology
Function and homology information


carboxylic acid transmembrane transport / carboxylic acid transmembrane transporter activity / hormone transport / cellular response to nonylphenol / cellular response to borneol / response to codeine / response to cyclosporin A / cellular response to mycotoxin / daunorubicin transport / positive regulation of response to drug ...carboxylic acid transmembrane transport / carboxylic acid transmembrane transporter activity / hormone transport / cellular response to nonylphenol / cellular response to borneol / response to codeine / response to cyclosporin A / cellular response to mycotoxin / daunorubicin transport / positive regulation of response to drug / terpenoid transport / ceramide floppase activity / negative regulation of sensory perception of pain / positive regulation of establishment of Sertoli cell barrier / regulation of intestinal absorption / cellular response to external biotic stimulus / response to quercetin / response to antineoplastic agent / ceramide translocation / floppase activity / Abacavir transmembrane transport / establishment of blood-retinal barrier / phosphatidylethanolamine flippase activity / protein localization to bicellular tight junction / external side of apical plasma membrane / phosphatidylcholine floppase activity / Atorvastatin ADME / xenobiotic transport across blood-brain barrier / response to thyroxine / establishment of blood-brain barrier / transepithelial transport / xenobiotic detoxification by transmembrane export across the plasma membrane / export across plasma membrane / P-type phospholipid transporter / ABC-type xenobiotic transporter / cellular response to L-glutamate / response to vitamin A / response to vitamin D / response to glycoside / ABC-type xenobiotic transporter activity / response to glucagon / intestinal absorption / response to alcohol / phospholipid translocation / Prednisone ADME / cellular response to antibiotic / cellular hyperosmotic salinity response / maintenance of blood-brain barrier / cellular response to alkaloid / efflux transmembrane transporter activity / xenobiotic transmembrane transporter activity / transmembrane transporter activity / ATPase-coupled transmembrane transporter activity / cellular response to dexamethasone stimulus / response to cadmium ion / transport across blood-brain barrier / lactation / xenobiotic metabolic process / regulation of chloride transport / response to progesterone / placenta development / stem cell proliferation / ABC-family proteins mediated transport / cellular response to estradiol stimulus / brush border membrane / female pregnancy / circadian rhythm / transmembrane transport / G2/M transition of mitotic cell cycle / cellular response to tumor necrosis factor / cellular response to lipopolysaccharide / response to hypoxia / apical plasma membrane / response to xenobiotic stimulus / ubiquitin protein ligase binding / cell surface / ATP hydrolysis activity / extracellular exosome / ATP binding / membrane / plasma membrane / cytoplasm
Similarity search - Function
Type 1 protein exporter / 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. ...Type 1 protein exporter / 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
ATP-dependent translocase ABCB1
Similarity search - Component
Biological speciesHomo sapiens (human) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.58 Å
AuthorsAlam A / Locher KP
Funding support Switzerland, United States, 3 items
OrganizationGrant numberCountry
Swiss National Science Foundation Switzerland
European Molecular Biology Organization Switzerland
National Institutes of Health United States
CitationJournal: Proc Natl Acad Sci U S A / Year: 2018
Title: Structure of a zosuquidar and UIC2-bound human-mouse chimeric ABCB1.
Authors: Amer Alam / Raphael Küng / Julia Kowal / Robert A McLeod / Nina Tremp / Eugenia V Broude / Igor B Roninson / Henning Stahlberg / Kaspar P Locher /
Abstract: The multidrug transporter ABCB1 (P-glycoprotein) is an ATP-binding cassette transporter that has a key role in protecting tissues from toxic insult and contributes to multidrug extrusion from cancer ...The multidrug transporter ABCB1 (P-glycoprotein) is an ATP-binding cassette transporter that has a key role in protecting tissues from toxic insult and contributes to multidrug extrusion from cancer cells. Here, we report the near-atomic resolution cryo-EM structure of nucleotide-free ABCB1 trapped by an engineered disulfide cross-link between the nucleotide-binding domains (NBDs) and bound to the antigen-binding fragment of the human-specific inhibitory antibody UIC2 and to the third-generation ABCB1 inhibitor zosuquidar. Our structure reveals the transporter in an occluded conformation with a central, enclosed, inhibitor-binding pocket lined by residues from all transmembrane (TM) helices of ABCB1. The pocket spans almost the entire width of the lipid membrane and is occupied exclusively by two closely interacting zosuquidar molecules. The external, conformational epitope facilitating UIC2 binding is also visualized, providing a basis for its inhibition of substrate efflux. Additional cryo-EM structures suggest concerted movement of TM helices from both halves of the transporters associated with closing the NBD gap, as well as zosuquidar binding. Our results define distinct recognition interfaces of ABCB1 inhibitory agents, which may be exploited for therapeutic purposes.
History
DepositionFeb 2, 2018-
Header (metadata) releaseFeb 21, 2018-
Map releaseFeb 21, 2018-
UpdateJul 9, 2025-
Current statusJul 9, 2025Processing site: PDBe / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.025
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by height
  • Surface level: 0.025
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6fn1
  • Surface level: 0.025
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol

Downloads & links

-
Map

FileDownload / File: emd_4281.map.gz / Format: CCP4 / Size: 163.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationZosuquidar complex of ABCB1HM-X. Final post-processed map after partial detergent belt removal.
Voxel sizeX=Y=Z: 0.84 Å
Density
Contour LevelBy AUTHOR: 0.025 / Movie #1: 0.025
Minimum - Maximum-0.13838151 - 0.22620861
Average (Standard dev.)-0.000044547967 (±0.004538118)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions350350350
Spacing350350350
CellA=B=C: 294.0 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.840.840.84
M x/y/z350350350
origin x/y/z0.0000.0000.000
length x/y/z294.000294.000294.000
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS350350350
D min/max/mean-0.1380.226-0.000

-
Supplemental data

-
Sample components

-
Entire : Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zo...

EntireName: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zosuquidar
Components
  • Complex: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zosuquidar
    • Complex: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zosuquidar
      • Protein or peptide: Human-mouse chimeric ABCB1 (ABCBHM)
    • Complex: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zosuquidar
      • Protein or peptide: UIC2 Antigen Binding Fragment Light chain
      • Protein or peptide: UIC2 Antigen Binding Fragment Heavy Chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: Zosuquidar

-
Supramolecule #1: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zo...

SupramoleculeName: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zosuquidar
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Molecular weightTheoretical: 195 KDa

-
Supramolecule #2: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zo...

SupramoleculeName: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zosuquidar
type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #3: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zo...

SupramoleculeName: Human-mouse chimeric ABCB1 (ABCB1HM) complex with UIC2 fab and zosuquidar
type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Mus musculus (house mouse)

-
Macromolecule #1: Human-mouse chimeric ABCB1 (ABCBHM)

MacromoleculeName: Human-mouse chimeric ABCB1 (ABCBHM) / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 137.719953 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: PAVSVLTMFR YAGWLDRLYM LVGTLAAIIH GVALPLMMLI FGEMTDIFAN AGNLEDLMSN ITNRSDINDT GFFMNLEEDM TTYAYYYTG IGAGVLIVAY IQVSFWLLAA GRQIHKIRQK FFHAIMNQEI GWFDVHDVGE LNTRLTDDVS KINEGIGDKI G MFFQAMAT ...String:
PAVSVLTMFR YAGWLDRLYM LVGTLAAIIH GVALPLMMLI FGEMTDIFAN AGNLEDLMSN ITNRSDINDT GFFMNLEEDM TTYAYYYTG IGAGVLIVAY IQVSFWLLAA GRQIHKIRQK FFHAIMNQEI GWFDVHDVGE LNTRLTDDVS KINEGIGDKI G MFFQAMAT FFGGFIIGFT RGWKLTLVIL AISPVLGLSA GIWAKILSSF TDKELHAYAK AGAVAEEVLA AIRTVIAFGG QK KELERYN NNLEEAKRLG IKKAITANIS MGAAFLLIYA SYALAFWYGT TLVLSGEYSI GQVLTVFFSV LIGAFSVGQA SPN IEAFAN ARGAAYEVFK IIDNKPSIDS FSKSGHKPDN IQGNLEFKNI HFSYPSRKEV QILKGLNLKV KSGQTVALVG NSGA GKSTT VQLMQRLYDP LDGMVSIDGQ DIRTINVRYL REIIGVVSQE PVLFATTIAE NIRYGREDVT MDEIEKAVKE ANAYD FIMK LPHQFDTLVG ERGAQLSGGQ KQRIAIARAL VRNPKILLLD EATCALDTES EAVVQAALDK AREGRTTIVI AHRLST VRN ADVIAGFDGG VIVEQGNHDE LMREKGIYFK LVMTQTAGNE IELGNEAAKS KDEIDNLDMS SKDSGSSLIR RRSTRKS IA GPHDQDRKLS TKEALDEDVP PASFWRILKL NSTEWPYFVV GIFVAIINGG LQPAFSVIFS KIIGVFTRID DPETKRQN S NLFSLLFLIL GIISFITFFL QGFTFGKAGE ILTKRLRYMV FKSMLRQDVS WFDDPKNTTG ALTTRLANDA AQVKGATGS RLAVIFQNIA NLGTGIIISF IYGWQLTLLL LAIVPIIAIA GVVEMKMLSG QALKDKKELE GSGKIATEAI ENFRTVVSLT REQKFETMY AQSLQIPYRN AMKKAHVFGI TFSFTQAMMY FSYAAAFRFG AYLVAHKLMS FEDVLLVFSA IVFGAMAVGQ V SSFAPDYA KATVSASHII RIIEKTPEID SYSTQGLKPN MLEGNVQFSG VVFNYPTRPS IPVLQGLSLE VKKGQTLALV GS SGAGKST VVQLLERFYD PMAGSVFLDG KEIKQLNVQW LRAQLGIVSQ EPILFDTSIA ENIAYGDNSR VVSYEEIVRA AKE ANIHQF IDSLPDKYNT RVGDKGTQLS GGQKQRIAIA RALVRQPHIL LLDEATCALD TESEKVVQEA LDKAREGRTT IVIA HRLST IQNADLIVVI QNGKVKEHGT HQQLLAQKGI YFSMVSVQAG AKRS

-
Macromolecule #2: UIC2 Antigen Binding Fragment Light chain

MacromoleculeName: UIC2 Antigen Binding Fragment Light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 24.321039 KDa
Recombinant expressionOrganism: Mus musculus (house mouse)
SequenceString: QVVMTQSPLS LPVSLGDQAS ISCRSSQSLL HSNGNTYLHW YLQKPGQSPK LLIYKVSNRF SGVPDRFSGS GSGTDFTLKI SRVEAEDLG VYFCSQSTHI PPWTFGGGTK LDIKRADAAP TVSIFPPSSE QLTSGGLSVV CFLNNFYPKD INVKWKIDGS E RQNGVLNS ...String:
QVVMTQSPLS LPVSLGDQAS ISCRSSQSLL HSNGNTYLHW YLQKPGQSPK LLIYKVSNRF SGVPDRFSGS GSGTDFTLKI SRVEAEDLG VYFCSQSTHI PPWTFGGGTK LDIKRADAAP TVSIFPPSSE QLTSGGLSVV CFLNNFYPKD INVKWKIDGS E RQNGVLNS WTDQDSKDST YSMSSTLTLT KDEYERHNSY TCEATHKTST SPIVKSFNRN EC

-
Macromolecule #3: UIC2 Antigen Binding Fragment Heavy Chain

MacromoleculeName: UIC2 Antigen Binding Fragment Heavy Chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 24.381281 KDa
Recombinant expressionOrganism: Mus musculus (house mouse)
SequenceString: EVQLQESGPE LVKTGASVKI SCKASGYSFS NYYIHWVKQS HGKSLEWIGF ISCYNGATFY NQKFKGKATF TVDNSSSTAY MKFNSLTFE DSAVYYCARL PIQFGNFYPM DYWGQGTTVT VSSAKTTAPS VYPLAPVCGD TTGSSVTLGC LVKGYFPEPV T LTWNSGSL ...String:
EVQLQESGPE LVKTGASVKI SCKASGYSFS NYYIHWVKQS HGKSLEWIGF ISCYNGATFY NQKFKGKATF TVDNSSSTAY MKFNSLTFE DSAVYYCARL PIQFGNFYPM DYWGQGTTVT VSSAKTTAPS VYPLAPVCGD TTGSSVTLGC LVKGYFPEPV T LTWNSGSL SSGVHTFPAV LQSDLYTLSS SVTVTSSTWP SQSITCNVAH PASSTKVDKK IEPRGPT

-
Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 3 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

-
Macromolecule #5: Zosuquidar

MacromoleculeName: Zosuquidar / type: ligand / ID: 5 / Number of copies: 2 / Formula: ZQU
Molecular weightTheoretical: 527.604 Da
Chemical component information

ChemComp-ZQU:
Zosuquidar / antineoplastic*YM

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 1.54 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

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.58 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 231969
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING

+
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