[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleStructural insights into binding-site access and ligand recognition by human ABCB1.
Journal, issue, pagesEMBO J, Vol. 44, Issue 4, Page 991-991006, Year 2025
Publish dateJan 13, 2025
AuthorsDevanshu Kurre / Phuoc X Dang / Le T M Le / Varun V Gadkari / Amer Alam /
PubMed AbstractABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it is able to recognize and transport a wide range of diverse substrates ...ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it is able to recognize and transport a wide range of diverse substrates remains poorly understood. Here we present cryo-EM structures of lipid-embedded human ABCB1 in conformationally distinct apo-, substrate-bound, inhibitor-bound, and nucleotide-trapped states at 3.4-3.9 Å resolution, in the absence of stabilizing antibodies or mutations. The substrate-binding site is located within one half of the molecule and, in the apo state, is obstructed by the transmembrane helix (TM) 4. Substrate and inhibitor binding are distinguished by major TM rearrangements and their ligand binding chemistry, with TM4 playing a central role in all conformational transitions. Furthermore, our data identify secondary structure-breaking residues that impart localized TM flexibility and asymmetry between the two transmembrane domains. The resulting structural changes and lipid interactions that are induced by substrate and inhibitor binding can predict substrate-binding profiles and may direct ABCB1 inhibitor design.
External linksEMBO J / PubMed:39806099 / PubMed Central
MethodsEM (single particle)
Resolution3.4 - 4.7 Å
Structure data

EMDB-45854, PDB-9cr8:
SapNP reconstituted human ABCB1
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-45903, PDB-9ctc:
SapNP reconstituted Human ABCB1 in complex with Zosuquidar and ATP/Mg
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-45904, PDB-9ctf:
SapNP Reconstituted Human ABCB1 bound to Taxol in presence of ATP
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-45906, PDB-9ctg:
SapNP Reconstituted Human ABCB1 bound to ATP gammaS
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-45931: HUMAN ABCB1 in SapNPs in complex with Taxol
Method: EM (single particle) / Resolution: 4.7 Å

EMDB-45932: HUMAN ABCB1 in SapNPs in complex with Zosuquidar
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-UPL:
UNKNOWN BRANCHED FRAGMENT OF PHOSPHOLIPID

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-ZQU:
Zosuquidar / antineoplastic*YM

ChemComp-TA1:
TAXOL / medication, chemotherapy*YM

ChemComp-MG:
Unknown entry

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogue*YM

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / TRANSLOCASE / ABCB1 / P-gp / apo form / nanoparticle / saposin A / MDR1 / p-glycoprotein / pgp / inhibitor bound / saposin / zosuquidar bound / substrate bound / taxol bound / php / ATPgammaS bound / non-hydrolysable nucleotide

+
About Yorodumi Papers

-
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 Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more