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- PDB-8g8w: Molecular mechanism of nucleotide inhibition of human uncoupling ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8g8w | |||||||||||||||||||||
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Title | Molecular mechanism of nucleotide inhibition of human uncoupling protein 1 | |||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / SLC25 / mitochondrial carrier / uncoupling | |||||||||||||||||||||
Function / homology | ![]() purine ribonucleotide binding / cellular response to dehydroepiandrosterone / The fatty acid cycling model / : / oxidative phosphorylation uncoupler activity / mitochondrial transmembrane transport / adaptive thermogenesis / cardiolipin binding / regulation of reactive oxygen species biosynthetic process / cellular response to cold ...purine ribonucleotide binding / cellular response to dehydroepiandrosterone / The fatty acid cycling model / : / oxidative phosphorylation uncoupler activity / mitochondrial transmembrane transport / adaptive thermogenesis / cardiolipin binding / regulation of reactive oxygen species biosynthetic process / cellular response to cold / cellular response to fatty acid / response to temperature stimulus / detection of maltose stimulus / long-chain fatty acid binding / maltose transport complex / diet induced thermogenesis / carbohydrate transport / proton transmembrane transporter activity / transmembrane transporter activity / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / brown fat cell differentiation / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / cellular response to hormone stimulus / proton transmembrane transport / response to cold / ATP-binding cassette (ABC) transporter complex / response to nutrient levels / cell chemotaxis / cellular response to reactive oxygen species / GDP binding / positive regulation of cold-induced thermogenesis / outer membrane-bounded periplasmic space / mitochondrial inner membrane / periplasmic space / DNA damage response / GTP binding / regulation of transcription by RNA polymerase II / mitochondrion / membrane Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() synthetic construct (others) ![]() ![]() | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||||||||||||||
![]() | Gogoi, P. / Jones, S.A. / Ruprecht, J.J. / King, M.S. / Lee, Y. / Zogg, T. / Pardon, E. / Chand, D. / Steimle, S. / Copeman, D. ...Gogoi, P. / Jones, S.A. / Ruprecht, J.J. / King, M.S. / Lee, Y. / Zogg, T. / Pardon, E. / Chand, D. / Steimle, S. / Copeman, D. / Cotrim, C.A. / Steyaert, J. / Crichton, P.G. / Moiseenkova-Bell, V. / Kunji, E.R.S. | |||||||||||||||||||||
Funding support | ![]() ![]() ![]()
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![]() | ![]() Title: Structural basis of purine nucleotide inhibition of human uncoupling protein 1. Authors: Scott A Jones / Prerana Gogoi / Jonathan J Ruprecht / Martin S King / Yang Lee / Thomas Zögg / Els Pardon / Deepak Chand / Stefan Steimle / Danielle M Copeman / Camila A Cotrim / Jan ...Authors: Scott A Jones / Prerana Gogoi / Jonathan J Ruprecht / Martin S King / Yang Lee / Thomas Zögg / Els Pardon / Deepak Chand / Stefan Steimle / Danielle M Copeman / Camila A Cotrim / Jan Steyaert / Paul G Crichton / Vera Moiseenkova-Bell / Edmund R S Kunji / ![]() ![]() ![]() Abstract: Mitochondrial uncoupling protein 1 (UCP1) gives brown adipose tissue of mammals its specialized ability to burn calories as heat for thermoregulation. When activated by fatty acids, UCP1 catalyzes ...Mitochondrial uncoupling protein 1 (UCP1) gives brown adipose tissue of mammals its specialized ability to burn calories as heat for thermoregulation. When activated by fatty acids, UCP1 catalyzes the leak of protons across the mitochondrial inner membrane, short-circuiting the mitochondrion to generate heat, bypassing ATP synthesis. In contrast, purine nucleotides bind and inhibit UCP1, regulating proton leak by a molecular mechanism that is unclear. We present the cryo-electron microscopy structure of the GTP-inhibited state of UCP1, which is consistent with its nonconducting state. The purine nucleotide cross-links the transmembrane helices of UCP1 with an extensive interaction network. Our results provide a structural basis for understanding the specificity and pH dependency of the regulatory mechanism. UCP1 has retained all of the key functional and structural features required for a mitochondrial carrier-like transport mechanism. The analysis shows that inhibitor binding prevents the conformational changes that UCP1 uses to facilitate proton leak. | |||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 167.8 KB | Display | ![]() |
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PDB format | ![]() | 125.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 40.9 KB | Display | |
Data in CIF | ![]() | 58 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 29857MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Antibody , 2 types, 2 molecules BC
#2: Antibody | Mass: 53453.910 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others), (gene. exp.) ![]() ![]() Gene: malE, b4034, JW3994 / Production host: ![]() ![]() |
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#3: Antibody | Mass: 54052.820 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others), (gene. exp.) ![]() ![]() Gene: malE, b4034, JW3994 / Production host: ![]() ![]() |
-Protein / Sugars , 2 types, 2 molecules A
#1: Protein | Mass: 33339.629 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#4: Polysaccharide | alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose Source method: isolated from a genetically manipulated source |
-Non-polymers , 2 types, 4 molecules ![](data/chem/img/GTP.gif)
![](data/chem/img/CDL.gif)
![](data/chem/img/CDL.gif)
#5: Chemical | ChemComp-GTP / |
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#6: Chemical |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Complex of human uncoupling protein 1 with two promacrobodies Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES | ||||||||||||||||||||||||||||||||||||||||
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Source (natural) | Organism: ![]() | ||||||||||||||||||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||
Buffer solution | pH: 6 | ||||||||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.14 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 72.9 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 203799 / Symmetry type: POINT |