[English] 日本語
Yorodumi
- EMDB-50894: Proton conductance by human uncoupling protein 1 is inhibited by ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-50894
TitleProton conductance by human uncoupling protein 1 is inhibited by both purine and pyrimidine nucleotides
Map data
Sample
  • Complex: UCP1 bound to UTP and in complex with two Pro-macrobodies
    • Protein or peptide: Mitochondrial brown fat uncoupling protein 1
    • Protein or peptide: CA9871
    • Protein or peptide: CA9865
  • Ligand: URIDINE 5'-TRIPHOSPHATE
  • Ligand: CARDIOLIPIN
KeywordsTRANSPORT PROTEIN
Function / homology
Function and homology information


purine ribonucleotide binding / cellular response to dehydroepiandrosterone / Mitochondrial Uncoupling / The fatty acid cycling model / oxidative phosphorylation uncoupler activity / mitochondrial transmembrane transport / adaptive thermogenesis / cardiolipin binding / cellular response to fatty acid / regulation of reactive oxygen species biosynthetic process ...purine ribonucleotide binding / cellular response to dehydroepiandrosterone / Mitochondrial Uncoupling / The fatty acid cycling model / oxidative phosphorylation uncoupler activity / mitochondrial transmembrane transport / adaptive thermogenesis / cardiolipin binding / cellular response to fatty acid / regulation of reactive oxygen species biosynthetic process / long-chain fatty acid binding / response to temperature stimulus / cellular response to cold / diet induced thermogenesis / proton transmembrane transporter activity / transmembrane transporter activity / brown fat cell differentiation / cellular response to hormone stimulus / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / proton transmembrane transport / response to cold / cellular response to reactive oxygen species / response to nutrient levels / GDP binding / positive regulation of cold-induced thermogenesis / mitochondrial inner membrane / regulation of transcription by RNA polymerase II / GTP binding / mitochondrion
Similarity search - Function
: / Mitochondrial carrier protein / Mitochondrial substrate/solute carrier / Mitochondrial carrier domain superfamily / Mitochondrial carrier protein / Solute carrier (Solcar) repeat profile.
Similarity search - Domain/homology
Mitochondrial brown fat uncoupling protein 1
Similarity search - Component
Biological speciesHomo sapiens (human) / Lama glama (llama)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.03 Å
AuthorsJones SA / Sowton AP / Lacabanne D / King MS / Palmer SM / Zogg T / Pardon E / Steyaert J / Ruprecht JJ / Kunji ERS
Funding support United Kingdom, European Union, Belgium, 3 items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom)MC_UU_00028/2 United Kingdom
European Union (EU)Instruct-ERIC/ESFRIEuropean Union
Research Foundation - Flanders (FWO) Belgium
CitationJournal: EMBO J / Year: 2025
Title: Proton conductance by human uncoupling protein 1 is inhibited by purine and pyrimidine nucleotides.
Authors: Scott A Jones / Alice P Sowton / Denis Lacabanne / Martin S King / Shane M Palmer / Thomas Zögg / Els Pardon / Jan Steyaert / Jonathan J Ruprecht / Edmund R S Kunji /
Abstract: Uncoupling protein 1 (UCP1, SLC25A7) is responsible for the thermogenic properties of brown adipose tissue. Upon fatty acid activation, UCP1 facilitates proton leakage, dissipating the mitochondrial ...Uncoupling protein 1 (UCP1, SLC25A7) is responsible for the thermogenic properties of brown adipose tissue. Upon fatty acid activation, UCP1 facilitates proton leakage, dissipating the mitochondrial proton motive force to release energy as heat. Purine nucleotides are considered to be the only inhibitors of UCP1 activity, binding to its central cavity to lock UCP1 in a proton-impermeable conformation. Here we show that pyrimidine nucleotides can also bind and inhibit its proton-conducting activity. All nucleotides bound in a pH-dependent manner, with the highest binding affinity observed for ATP, followed by dTTP, UTP, GTP and CTP. We also determined the structural basis of UTP binding to UCP1, showing that binding of purine and pyrimidine nucleotides follows the same molecular principles. We find that the closely related mitochondrial dicarboxylate carrier (SLC25A10) and oxoglutarate carrier (SLC25A11) have many cavity residues in common, but do not bind nucleotides. Thus, while UCP1 has evolved from dicarboxylate carriers, no selection for nucleobase specificity has occurred, highlighting the importance of the pH-dependent nucleotide binding mechanism mediated via the phosphate moieties.
History
DepositionJul 5, 2024-
Header (metadata) releaseMar 5, 2025-
Map releaseMar 5, 2025-
UpdateJul 2, 2025-
Current statusJul 2, 2025Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_50894.png

Downloads & links

-
Map

FileDownload / File: emd_50894.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.65 Å/pix.
x 512 pix.
= 330.24 Å		0.65 Å/pix.
x 512 pix.
= 330.24 Å		0.65 Å/pix.
x 512 pix.
= 330.24 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.645 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.6927433 - 0.8379715
Average (Standard dev.)-0.000052878266 (±0.007173175)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 330.24 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_50894_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_50894_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : UCP1 bound to UTP and in complex with two Pro-macrobodies

EntireName: UCP1 bound to UTP and in complex with two Pro-macrobodies
Components
  • Complex: UCP1 bound to UTP and in complex with two Pro-macrobodies
    • Protein or peptide: Mitochondrial brown fat uncoupling protein 1
    • Protein or peptide: CA9871
    • Protein or peptide: CA9865
  • Ligand: URIDINE 5'-TRIPHOSPHATE
  • Ligand: CARDIOLIPIN

-
Supramolecule #1: UCP1 bound to UTP and in complex with two Pro-macrobodies

SupramoleculeName: UCP1 bound to UTP and in complex with two Pro-macrobodies
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Mitochondrial brown fat uncoupling protein 1

MacromoleculeName: Mitochondrial brown fat uncoupling protein 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 33.339629 KDa
Recombinant expressionOrganism: Saccharomyces cerevisiae (brewer's yeast)
SequenceString: TSEDGGLTAS DVHPTLGVQL FSAGIAACLA DVITFPLDTA KVRLQVQGEC PTSSVIRYKG VLGTITAVVK TEGRMKLYSG LPAGLQRQI SSASLRIGLY DTVQEFLTAG KETAPSLGSK ILAGLTTGGV AVFIGQPTEV VKVRLQAQSH LHGIKPRYTG T YNAYRIIA ...String:
TSEDGGLTAS DVHPTLGVQL FSAGIAACLA DVITFPLDTA KVRLQVQGEC PTSSVIRYKG VLGTITAVVK TEGRMKLYSG LPAGLQRQI SSASLRIGLY DTVQEFLTAG KETAPSLGSK ILAGLTTGGV AVFIGQPTEV VKVRLQAQSH LHGIKPRYTG T YNAYRIIA TTEGLTGLWK GTTPNLMRSV IINCTELVTY DLMKEAFVKN NILADDVPCH LVSALIAGFC ATAMSSPVDV VK TRFINSP PGQYKSVPNC AMKVFTNEGP TAFFKGLVPS FLRLGSWNVI MFVCFEQLKR ELSKSRQTMD CAT

UniProtKB: Mitochondrial brown fat uncoupling protein 1

-
Macromolecule #2: CA9871

MacromoleculeName: CA9871 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 13.423773 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
QVQLVESGGG LVQAGDSLRL SCAASGLTLK NYAMGWFRQA PGKEHEFVAV ISWSGSGTSY ADSVEGRFTI SRDNAKNTAF LQMSSLKPE DTAVYYCAAR DGGYGSRWPD EYTYWGQGTQ VTVPP

-
Macromolecule #3: CA9865

MacromoleculeName: CA9865 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 14.02268 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
QVQLVESGGG LVQAGGSLRL SCAPSGRTSS TYTMGWFRQA PGKEREFVAA ISWTGTPYYA DSVKGRFTIS RDNAKNTVYL QMNSLKPED TAVYYCAAAR PGLFIFVSDY ARTAKYDYWG QGTQVTVPP

-
Macromolecule #4: URIDINE 5'-TRIPHOSPHATE

MacromoleculeName: URIDINE 5'-TRIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 1 / Formula: UTP
Molecular weightTheoretical: 484.141 Da
Chemical component information

ChemComp-UTP:
URIDINE 5'-TRIPHOSPHATE / UTP*YM

-
Macromolecule #5: CARDIOLIPIN

MacromoleculeName: CARDIOLIPIN / type: ligand / ID: 5 / Number of copies: 3 / Formula: CDL
Molecular weightTheoretical: 1.464043 KDa
Chemical component information

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration3 mg/mL
BufferpH: 6
Component:
ConcentrationName
20.0 mMMES
150.0 mMNaCl
0.02 %Lauryl maltose neopentyl glycol
0.02 mg/mLTetraoleoyl cardiolipin
1.0 mMTCEP
2.0 mMMaltose
2.0 mMUTP
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

8g8w

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.03 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 705820
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
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