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| | ==Cryo-EM structure of respiratory complex I from Yarrowia lipolytica at 3.2 A resolution== | | ==Cryo-EM structure of respiratory complex I from Yarrowia lipolytica at 3.2 A resolution== |
| - | <StructureSection load='6rfr' size='340' side='right'caption='[[6rfr]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <SX load='6rfr' size='340' side='right' viewer='molstar' caption='[[6rfr]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6rfr]] is a 42 chain structure with sequence from [http://en.wikipedia.org/wiki/Yarrowia_lipolytica Yarrowia lipolytica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RFR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RFR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rfr]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Yarrowia_lipolytica Yarrowia lipolytica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RFR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RFR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene>, <scene name='pdbligand=CPL:1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>CPL</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=LMN:LAURYL+MALTOSE+NEOPENTYL+GLYCOL'>LMN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=PLC:DIUNDECYL+PHOSPHATIDYL+CHOLINE'>PLC</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=T7X:PHOSPHATIDYLINOSITOL'>T7X</scene>, <scene name='pdbligand=UQ9:UBIQUINONE-9'>UQ9</scene>, <scene name='pdbligand=ZMP:S-[2-({N-[(2S)-2-HYDROXY-3,3-DIMETHYL-4-(PHOSPHONOOXY)BUTANOYL]-BETA-ALANYL}AMINO)ETHYL]+TETRADECANETHIOATE'>ZMP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NADH_dehydrogenase NADH dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.99.3 1.6.99.3] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene>, <scene name='pdbligand=CPL:1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>CPL</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=LMN:LAURYL+MALTOSE+NEOPENTYL+GLYCOL'>LMN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=PLC:DIUNDECYL+PHOSPHATIDYL+CHOLINE'>PLC</scene>, <scene name='pdbligand=T7X:PHOSPHATIDYLINOSITOL'>T7X</scene>, <scene name='pdbligand=UQ9:UBIQUINONE-9'>UQ9</scene>, <scene name='pdbligand=ZMP:S-[2-({N-[(2S)-2-HYDROXY-3,3-DIMETHYL-4-(PHOSPHONOOXY)BUTANOYL]-BETA-ALANYL}AMINO)ETHYL]+TETRADECANETHIOATE'>ZMP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6rfr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rfr OCA], [http://pdbe.org/6rfr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rfr RCSB], [http://www.ebi.ac.uk/pdbsum/6rfr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rfr ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6rfr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rfr OCA], [https://pdbe.org/6rfr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rfr RCSB], [https://www.ebi.ac.uk/pdbsum/6rfr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rfr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q9UUU2_YARLL Q9UUU2_YARLL]] Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain.[RuleBase:RU364066] [[http://www.uniprot.org/uniprot/A0A1D8NG21_YARLL A0A1D8NG21_YARLL]] Carrier of the growing fatty acid chain in fatty acid biosynthesis.[RuleBase:RU000722] [[http://www.uniprot.org/uniprot/NU6M_YARLI NU6M_YARLI]] Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. [[http://www.uniprot.org/uniprot/A0A1H6PXT9_YARLL A0A1H6PXT9_YARLL]] Carrier of the growing fatty acid chain in fatty acid biosynthesis.[RuleBase:RU000722] [[http://www.uniprot.org/uniprot/A0A1D8N5V2_YARLL A0A1D8N5V2_YARLL]] Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.[RuleBase:RU363103] [[http://www.uniprot.org/uniprot/S5TF58_YARLL S5TF58_YARLL]] Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.[RuleBase:RU003404] [[http://www.uniprot.org/uniprot/NU4LM_YARLI NU4LM_YARLI]] Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. [[http://www.uniprot.org/uniprot/S5TMP9_YARLL S5TMP9_YARLL]] Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.[RuleBase:RU003297] [[http://www.uniprot.org/uniprot/S5TMS4_YARLL S5TMS4_YARLL]] Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.[RuleBase:RU003640][SAAS:SAAS01013641] [[http://www.uniprot.org/uniprot/A0A371C2D0_YARLL A0A371C2D0_YARLL]] Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.[PIRNR:PIRNR017016] | + | [https://www.uniprot.org/uniprot/F2Z6F1_YARLI F2Z6F1_YARLI] |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Respiratory complex I is a redox-driven proton pump, accounting for a large part of the electrochemical gradient that powers mitochondrial adenosine triphosphate synthesis. Complex I dysfunction is associated with severe human diseases. Assembly of the one-megadalton complex I in the inner mitochondrial membrane requires assembly factors and chaperones. We have determined the structure of complex I from the aerobic yeast Yarrowia lipolytica by electron cryo-microscopy at 3.2-A resolution. A ubiquinone molecule was identified in the access path to the active site. The electron cryo-microscopy structure indicated an unusual lipid-protein arrangement at the junction of membrane and matrix arms that was confirmed by molecular simulations. The structure of a complex I mutant and an assembly intermediate provide detailed molecular insights into the cause of a hereditary complex I-linked disease and complex I assembly in the inner mitochondrial membrane. |
| | + | |
| | + | High-resolution cryo-EM structures of respiratory complex I: Mechanism, assembly, and disease.,Parey K, Haapanen O, Sharma V, Kofeler H, Zullig T, Prinz S, Siegmund K, Wittig I, Mills DJ, Vonck J, Kuhlbrandt W, Zickermann V Sci Adv. 2019 Dec 11;5(12):eaax9484. doi: 10.1126/sciadv.aax9484. eCollection, 2019 Dec. PMID:31844670<ref>PMID:31844670</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 6rfr" style="background-color:#fffaf0;"></div> |
| | + | == References == |
| | + | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: NADH dehydrogenase]] | |
| | [[Category: Yarrowia lipolytica]] | | [[Category: Yarrowia lipolytica]] |
| - | [[Category: Parey, K]] | + | [[Category: Parey K]] |
| - | [[Category: Vonck, J]] | + | [[Category: Vonck J]] |
| - | [[Category: Complex i]]
| + | |
| - | [[Category: Mitochondrion proton pumping]]
| + | |
| - | [[Category: Nadh dehydrogenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Ubiquinone]]
| + | |
| Structural highlights
Function
F2Z6F1_YARLI
Publication Abstract from PubMed
Respiratory complex I is a redox-driven proton pump, accounting for a large part of the electrochemical gradient that powers mitochondrial adenosine triphosphate synthesis. Complex I dysfunction is associated with severe human diseases. Assembly of the one-megadalton complex I in the inner mitochondrial membrane requires assembly factors and chaperones. We have determined the structure of complex I from the aerobic yeast Yarrowia lipolytica by electron cryo-microscopy at 3.2-A resolution. A ubiquinone molecule was identified in the access path to the active site. The electron cryo-microscopy structure indicated an unusual lipid-protein arrangement at the junction of membrane and matrix arms that was confirmed by molecular simulations. The structure of a complex I mutant and an assembly intermediate provide detailed molecular insights into the cause of a hereditary complex I-linked disease and complex I assembly in the inner mitochondrial membrane.
High-resolution cryo-EM structures of respiratory complex I: Mechanism, assembly, and disease.,Parey K, Haapanen O, Sharma V, Kofeler H, Zullig T, Prinz S, Siegmund K, Wittig I, Mills DJ, Vonck J, Kuhlbrandt W, Zickermann V Sci Adv. 2019 Dec 11;5(12):eaax9484. doi: 10.1126/sciadv.aax9484. eCollection, 2019 Dec. PMID:31844670[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Parey K, Haapanen O, Sharma V, Kofeler H, Zullig T, Prinz S, Siegmund K, Wittig I, Mills DJ, Vonck J, Kuhlbrandt W, Zickermann V. High-resolution cryo-EM structures of respiratory complex I: Mechanism, assembly, and disease. Sci Adv. 2019 Dec 11;5(12):eaax9484. doi: 10.1126/sciadv.aax9484. eCollection, 2019 Dec. PMID:31844670 doi:http://dx.doi.org/10.1126/sciadv.aax9484
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