[English] 日本語
Yorodumi
- EMDB-4391: Structure of P-glycoprotein(ABCB1) in the post-hydrolytic state -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-4391
TitleStructure of P-glycoprotein(ABCB1) in the post-hydrolytic state
Map dataShows the additional density compared to the core domains as discussed in the manuscript. Corresponds to a volume enclosed of 160x10^3 Angstrom cubed.
Sample
  • Complex: mouse P-glycoprotein
    • Protein or peptide: Multidrug resistance protein 1AMultiple drug resistance
Function / homology
Function and homology information


hormone transport / cellular response to borneol / response to codeine / response to cyclosporin A / Atorvastatin ADME / cellular response to mycotoxin / daunorubicin transport / positive regulation of response to drug / response to quercetin / cellular response to external biotic stimulus ...hormone transport / cellular response to borneol / response to codeine / response to cyclosporin A / Atorvastatin ADME / cellular response to mycotoxin / daunorubicin transport / positive regulation of response to drug / response to quercetin / cellular response to external biotic stimulus / regulation of intestinal absorption / response to antineoplastic agent / Prednisone ADME / positive regulation of establishment of Sertoli cell barrier / ceramide translocation / terpenoid transport / ceramide floppase activity / response to glycoside / carboxylic acid transmembrane transport / carboxylic acid transmembrane transporter activity / floppase activity / establishment of blood-retinal barrier / protein localization to bicellular tight junction / regulation of response to osmotic stress / cellular response to L-glutamate / ABC-family proteins mediated transport / establishment of blood-brain barrier / response to thyroxine / phosphatidylcholine floppase activity / phosphatidylethanolamine flippase activity / xenobiotic transport across blood-brain barrier / xenobiotic detoxification by transmembrane export across the plasma membrane / export across plasma membrane / response to vitamin D / ABC-type xenobiotic transporter / intercellular canaliculus / transepithelial transport / P-type phospholipid transporter / ABC-type xenobiotic transporter activity / response to vitamin A / response to glucagon / intestinal absorption / phospholipid translocation / cellular response to antibiotic / maintenance of blood-brain barrier / cellular hyperosmotic salinity response / cellular response to alkaloid / xenobiotic transmembrane transporter activity / efflux transmembrane transporter activity / transmembrane transporter activity / ATPase-coupled transmembrane transporter activity / response to cadmium ion / lactation / cellular response to dexamethasone stimulus / placenta development / regulation of chloride transport / stem cell proliferation / cellular response to estradiol stimulus / brush border membrane / circadian rhythm / G2/M transition of mitotic cell cycle / cellular response to tumor necrosis factor / cellular response to lipopolysaccharide / response to hypoxia / response to xenobiotic stimulus / apical plasma membrane / ubiquitin protein ligase binding / cell surface / ATP hydrolysis activity / 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 speciesMus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 7.9 Å
AuthorsFord RC / Thonghin N / Collins RF / Barbieri A / Shafi T / Siebert A
CitationJournal: BMC Struct Biol / Year: 2018
Title: Novel features in the structure of P-glycoprotein (ABCB1) in the post-hydrolytic state as determined at 7.9 Å resolution.
Authors: Nopnithi Thonghin / Richard F Collins / Alessandro Barbieri / Talha Shafi / Alistair Siebert / Robert C Ford /
Abstract: BACKGROUND: P-glycoprotein (ABCB1) is an ATP-binding cassette transporter that plays an important role in the clearance of drugs and xenobiotics and is associated with multi-drug resistance in cancer. ...BACKGROUND: P-glycoprotein (ABCB1) is an ATP-binding cassette transporter that plays an important role in the clearance of drugs and xenobiotics and is associated with multi-drug resistance in cancer. Although several P-glycoprotein structures are available, these are either at low resolution, or represent mutated and/or quiescent states of the protein.
RESULTS: In the post-hydrolytic state the structure of the wild-type protein has been resolved at about 8 Å resolution. The cytosolic nucleotide-binding domains (NBDs) are separated but ADP ...RESULTS: In the post-hydrolytic state the structure of the wild-type protein has been resolved at about 8 Å resolution. The cytosolic nucleotide-binding domains (NBDs) are separated but ADP remains bound, especially at the first NBD. Gaps in the transmembrane domains (TMDs) that connect to an inner hydrophilic cavity are filled by density emerging from the annular detergent micelle. The NBD-TMD linker is partly resolved, being located between the NBDs and close to the Signature regions involved in cooperative NBD dimerization. This, and the gap-filling detergent suggest steric impediment to NBD dimerization in the post-hydrolytic state. Two central regions of density lie in two predicted drug-binding sites, implying that the protein may adventitiously bind hydrophobic substances even in the post-hydrolytic state. The previously unresolved N-terminal extension was observed, and the data suggests these 30 residues interact with the headgroup region of the lipid bilayer.
CONCLUSION: The structural data imply that (i) a low basal ATPase activity is ensured by steric blockers of NBD dimerization and (ii) allocrite access to the central cavity may be structurally linked ...CONCLUSION: The structural data imply that (i) a low basal ATPase activity is ensured by steric blockers of NBD dimerization and (ii) allocrite access to the central cavity may be structurally linked to NBD dimerization, giving insights into the mechanism of drug-stimulation of P-glycoprotein activity.
History
DepositionApr 23, 2018-
Header (metadata) releaseMay 23, 2018-
Map releaseMay 23, 2018-
UpdateApr 3, 2019-
Current statusApr 3, 2019Processing site: PDBe / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.03
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by height
  • Surface level: 0.03
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6gdi
  • Surface level: 0.03
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6q81
  • Surface level: 0.03
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6gdi
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_4391.png

Downloads & links

-
Map

FileDownload / File: emd_4391.map.gz / Format: CCP4 / Size: 14.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationShows the additional density compared to the core domains as discussed in the manuscript. Corresponds to a volume enclosed of 160x10^3 Angstrom cubed.
Voxel sizeX=Y=Z: 1.06 Å
Density
Contour LevelBy AUTHOR: 0.03 / Movie #1: 0.03
Minimum - Maximum-0.14932539 - 0.21956994
Average (Standard dev.)0.0027335607 (±0.012639964)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin303030
Dimensions156156156
Spacing156156156
CellA=B=C: 165.35999 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.061.061.06
M x/y/z156156156
origin x/y/z0.0000.0000.000
length x/y/z165.360165.360165.360
α/β/γ90.00090.00090.000
start NX/NY/NZ-383-383-383
NX/NY/NZ768768768
MAP C/R/S123
start NC/NR/NS303030
NC/NR/NS156156156
D min/max/mean-0.1490.2200.003

-
Supplemental data

-
Sample components

-
Entire : mouse P-glycoprotein

EntireName: mouse P-glycoprotein
Components
  • Complex: mouse P-glycoprotein
    • Protein or peptide: Multidrug resistance protein 1AMultiple drug resistance

-
Supramolecule #1: mouse P-glycoprotein

SupramoleculeName: mouse P-glycoprotein / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Mus musculus (house mouse)
Recombinant expressionOrganism: Komagataella pastoris (fungus)

-
Macromolecule #1: Multidrug resistance protein 1A

MacromoleculeName: Multidrug resistance protein 1A / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: xenobiotic-transporting ATPase
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 141.877875 KDa
Recombinant expressionOrganism: Komagataella pastoris (fungus)
SequenceString: MELEEDLKGR ADKNFSKMGK KSKKEKKEKK PAVSVLTMFR YAGWLDRLYM LVGTLAAIIH GVALPLMMLI FGDMTDSFAS VGNVSKNST NMSEADKRAM FAKLEEEMTT YAYYYTGIGA GVLIVAYIQV SFWCLAAGRQ IHKIRQKFFH AIMNQEIGWF D VHDVGELN ...String:
MELEEDLKGR ADKNFSKMGK KSKKEKKEKK PAVSVLTMFR YAGWLDRLYM LVGTLAAIIH GVALPLMMLI FGDMTDSFAS VGNVSKNST NMSEADKRAM FAKLEEEMTT YAYYYTGIGA GVLIVAYIQV SFWCLAAGRQ IHKIRQKFFH AIMNQEIGWF D VHDVGELN TRLTDDVSKI NEGIGDKIGM FFQAMATFFG GFIIGFTRGW KLTLVILAIS PVLGLSAGIW AKILSSFTDK EL HAYAKAG AVAEEVLAAI RTVIAFGGQK KELERYNNNL EEAKRLGIKK AITANISMGA AFLLIYASYA LAFWYGTSLV ISK EYSIGQ VLTVFFSVLI GAFSVGQASP NIEAFANARG AAYEVFKIID NKPSIDSFSK SGHKPDNIQG NLEFKNIHFS YPSR KEVQI LKGLNLKVKS GQTVALVGNS GCGKSTTVQL MQRLYDPLDG MVSIDGQDIR TINVRYLREI IGVVSQEPVL FATTI AENI RYGREDVTMD EIEKAVKEAN AYDFIMKLPH QFDTLVGERG AQLSGGQKQR IAIARALVRN PKILLLDEAT SALDTE SEA VVQAALDKAR EGRTTIVIAH RLSTVRNADV IAGFDGGVIV EQGNHDELMR EKGIYFKLVM TQTAGNEIEL GNEACKS KD EIDNLDMSSK DSGSSLIRRR STRKSICGPH DQDRKLSTKE ALDEDVPPAS FWRILKLNST EWPYFVVGIF CAIINGGL Q PAFSVIFSKV VGVFTNGGPP ETQRQNSNLF SLLFLILGII SFITFFLQGF TFGKAGEILT KRLRYMVFKS MLRQDVSWF DDPKNTTGAL TTRLANDAAQ VKGATGSRLA VIFQNIANLG TGIIISLIYG WQLTLLLLAI VPIIAIAGVV EMKMLSGQAL KDKKELEGS GKIATEAIEN FRTVVSLTRE QKFETMYAQS LQIPYRNAMK KAHVFGITFS FTQAMMYFSY AACFRFGAYL V TQQLMTFE NVLLVFSAIV FGAMAVGQVS SFAPDYAKAT VSASHIIRII EKTPEIDSYS TQGLKPNMLE GNVQFSGVVF NY PTRPSIP VLQGLSLEVK KGQTLALVGS SGCGKSTVVQ LLERFYDPMA GSVFLDGKEI KQLNVQWLRA QLGIVSQEPI LFD CSIAEN IAYGDNSRVV SYEEIVRAAK EANIHQFIDS LPDKYNTRVG DKGTQLSGGQ KQRIAIARAL VRQPHILLLD EATS ALDTE SEKVVQEALD KAREGRTCIV IAHRLSTIQN ADLIVVIQNG KVKEHGTHQQ LLAQKGIYFS MVSVQAGAKR SLEHH HHHH

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration1.1 mg/mL
BufferpH: 8
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 70.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

CTF correctionSoftware - Name: Gctf
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
Final reconstructionNumber classes used: 18 / Resolution.type: BY AUTHOR / Resolution: 7.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 135357
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

4ksb


Chain - Chain ID: a / Chain - Residue range: 33-1271
RefinementProtocol: FLEXIBLE FIT
Output model

PDB-6gdi:
Structure of P-glycoprotein(ABCB1) in the post-hydrolytic state

PDB-6q81:
Structure of P-glycoprotein(ABCB1) in the post-hydrolytic state

+
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