[English] 日本語
Yorodumi
- EMDB-32951: Cryo-EM structure of human ABCD1 E630Q in the presence of ATP in ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-32951
TitleCryo-EM structure of human ABCD1 E630Q in the presence of ATP in inward-facing state
Map data
Sample
  • Complex: Cryo-EM structure of human ABCD1 E630Q in the presence of ATP in inward-facing state
    • Protein or peptide: ATP-binding cassette sub-family D member 1
  • Ligand: ADENOSINE-5'-TRIPHOSPHATE
Keywordscomplex / membrane protein / ligand / STRUCTURAL PROTEIN
Function / homology
Function and homology information


ABC-type fatty-acyl-CoA transporter activity / peroxisomal membrane transport / very long-chain fatty-acyl-CoA catabolic process / very long-chain fatty acyl-CoA hydrolase activity / positive regulation of unsaturated fatty acid biosynthetic process / Linoleic acid (LA) metabolism / Defective ABCD1 causes ALD / alpha-linolenic acid metabolic process / long-chain fatty acid catabolic process / long-chain fatty acid import into peroxisome ...ABC-type fatty-acyl-CoA transporter activity / peroxisomal membrane transport / very long-chain fatty-acyl-CoA catabolic process / very long-chain fatty acyl-CoA hydrolase activity / positive regulation of unsaturated fatty acid biosynthetic process / Linoleic acid (LA) metabolism / Defective ABCD1 causes ALD / alpha-linolenic acid metabolic process / long-chain fatty acid catabolic process / long-chain fatty acid import into peroxisome / very long-chain fatty acid catabolic process / alpha-linolenic acid (ALA) metabolism / regulation of fatty acid beta-oxidation / Beta-oxidation of very long chain fatty acids / Class I peroxisomal membrane protein import / very long-chain fatty acid metabolic process / sterol homeostasis / peroxisome organization / regulation of mitochondrial depolarization / ABC transporters in lipid homeostasis / myelin maintenance / fatty acyl-CoA hydrolase activity / regulation of cellular response to oxidative stress / Hydrolases; Acting on ester bonds; Thioester hydrolases / positive regulation of fatty acid beta-oxidation / linoleic acid metabolic process / regulation of oxidative phosphorylation / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / fatty acid elongation / peroxisomal membrane / long-chain fatty acid transmembrane transporter activity / fatty acid beta-oxidation / ATPase-coupled transmembrane transporter activity / negative regulation of cytokine production involved in inflammatory response / fatty acid homeostasis / negative regulation of reactive oxygen species biosynthetic process / neuron projection maintenance / mitochondrial membrane / ADP binding / peroxisome / protein heterodimerization activity / lysosomal membrane / endoplasmic reticulum membrane / perinuclear region of cytoplasm / enzyme binding / protein homodimerization activity / ATP hydrolysis activity / ATP binding / identical protein binding / membrane / cytoplasm / cytosol
Similarity search - Function
Peroxysomal long chain fatty acyl transporter / ABC transporter transmembrane region 2 / 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. ...Peroxysomal long chain fatty acyl transporter / ABC transporter transmembrane region 2 / 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-binding cassette sub-family D member 1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsChao X / Li-Na J / Lin T
Funding support China, 4 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)31770897 China
National Natural Science Foundation of China (NSFC)81801294 China
Other government2017YFA0505300
Other government2021YFH0141
CitationJournal: Signal Transduct Target Ther / Year: 2023
Title: Structural insights into substrate recognition and translocation of human peroxisomal ABC transporter ALDP.
Authors: Chao Xiong / Li-Na Jia / Wei-Xi Xiong / Xin-Tong Wu / Liu-Lin Xiong / Ting-Hua Wang / Dong Zhou / Zhen Hong / Zheng Liu / Lin Tang /
Abstract: Dysfunctions of ATP-binding cassette, subfamily D, member 1 (ABCD1) cause X-linked adrenoleukodystrophy, a rare neurodegenerative disease that affects all human tissues. Residing in the peroxisome ...Dysfunctions of ATP-binding cassette, subfamily D, member 1 (ABCD1) cause X-linked adrenoleukodystrophy, a rare neurodegenerative disease that affects all human tissues. Residing in the peroxisome membrane, ABCD1 plays a role in the translocation of very long-chain fatty acids for their β-oxidation. Here, the six cryo-electron microscopy structures of ABCD1 in four distinct conformational states were presented. In the transporter dimer, two transmembrane domains form the substrate translocation pathway, and two nucleotide-binding domains form the ATP-binding site that binds and hydrolyzes ATP. The ABCD1 structures provide a starting point for elucidating the substrate recognition and translocation mechanism of ABCD1. Each of the four inward-facing structures of ABCD1 has a vestibule that opens to the cytosol with variable sizes. Hexacosanoic acid (C26:0)-CoA substrate binds to the transmembrane domains (TMDs) and stimulates the ATPase activity of the nucleotide-binding domains (NBDs). W339 from the transmembrane helix 5 (TM5) is essential for binding substrate and stimulating ATP hydrolysis by substrate. ABCD1 has a unique C-terminal coiled-coil domain that negatively modulates the ATPase activity of the NBDs. Furthermore, the structure of ABCD1 in the outward-facing state indicates that ATP molecules pull the two NBDs together and open the TMDs to the peroxisomal lumen for substrate release. The five structures provide a view of the substrate transport cycle and mechanistic implication for disease-causing mutations.
History
DepositionFeb 24, 2022-
Header (metadata) releaseMar 22, 2023-
Map releaseMar 22, 2023-
UpdateJun 26, 2024-
Current statusJun 26, 2024Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_32951.png

Downloads & links

-
Map

FileDownload / File: emd_32951.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.83 Å
Density
Contour LevelBy AUTHOR: 0.14
Minimum - Maximum-1.2105678 - 1.8200259
Average (Standard dev.)-0.0003912548 (±0.025783366)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 332.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Sample components

-
Entire : Cryo-EM structure of human ABCD1 E630Q in the presence of ATP in ...

EntireName: Cryo-EM structure of human ABCD1 E630Q in the presence of ATP in inward-facing state
Components
  • Complex: Cryo-EM structure of human ABCD1 E630Q in the presence of ATP in inward-facing state
    • Protein or peptide: ATP-binding cassette sub-family D member 1
  • Ligand: ADENOSINE-5'-TRIPHOSPHATE

-
Supramolecule #1: Cryo-EM structure of human ABCD1 E630Q in the presence of ATP in ...

SupramoleculeName: Cryo-EM structure of human ABCD1 E630Q in the presence of ATP in inward-facing state
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: ATP-binding cassette sub-family D member 1

MacromoleculeName: ATP-binding cassette sub-family D member 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
EC number: Hydrolases; Acting on ester bonds; Thioester hydrolases
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 85.194125 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDYKDDDDKG SENLYFQSMP VLSRPRPWRG NTLKRTAVLL ALAAYGAHKV YPLVRQCLAP ARGLQAPAGE PTQEASGVAA AKAGMNRVF LQRLLWLLRL LFPRVLCRET GLLALHSAAL VSRTFLSVYV ARLDGRLARC IVRKDPRAFG WQLLQWLLIA L PATFVNSA ...String:
MDYKDDDDKG SENLYFQSMP VLSRPRPWRG NTLKRTAVLL ALAAYGAHKV YPLVRQCLAP ARGLQAPAGE PTQEASGVAA AKAGMNRVF LQRLLWLLRL LFPRVLCRET GLLALHSAAL VSRTFLSVYV ARLDGRLARC IVRKDPRAFG WQLLQWLLIA L PATFVNSA IRYLEGQLAL SFRSRLVAHA YRLYFSQQTY YRVSNMDGRL RNPDQSLTED VVAFAASVAH LYSNLTKPLL DV AVTSYTL LRAARSRGAG TAWPSAIAGL VVFLTANVLR AFSPKFGELV AEEARRKGEL RYMHSRVVAN SEEIAFYGGH EVE LALLQR SYQDLASQIN LILLERLWYV MLEQFLMKYV WSASGLLMVA VPIITATGYS ESDAEAVKKA ALEKKEEELV SERT EAFTI ARNLLTAAAD AIERIMSSYK EVTELAGYTA RVHEMFQVFE DVQRCHFKRP RELEDAQAGS GTIGRSGVRV EGPLK IRGQ VVDVEQGIIC ENIPIVTPSG EVVVASLNIR VEEGMHLLIT GPNGCGKSSL FRILGGLWPT YGGVLYKPPP QRMFYI PQR PYMSVGSLRD QVIYPDSVED MQRKGYSEQD LEAILDVVHL HHILQREGGW EAMCDWKDVL SGGEKQRIGM ARMFYHR PK YALLDQCTSA VSIDVEGKIF QAAKDAGIAL LSITHRPSLW KYHTHLLQFD GEGGWKFEKL DSAARLSLTE EKQRLEQQ L AGIPKMQRRL QELCQILGEA VAPAHVPAPS PQGPGGLQGA ST

UniProtKB: ATP-binding cassette sub-family D member 1

-
Macromolecule #2: ADENOSINE-5'-TRIPHOSPHATE

MacromoleculeName: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 2 / Number of copies: 2 / Formula: ATP
Molecular weightTheoretical: 507.181 Da
Chemical component information

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

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation state3D array

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI EAGLE (4k x 4k) / Average electron dose: 66.5 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 636285
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: COMMON LINE

+
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://pdbjlvh1.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