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| | ==Structural basis for GTP hydrolysis and conformational change of mitofusin 1 in mediating mitochondrial fusion== | | ==Structural basis for GTP hydrolysis and conformational change of mitofusin 1 in mediating mitochondrial fusion== |
| - | <StructureSection load='5yew' size='340' side='right' caption='[[5yew]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='5yew' size='340' side='right'caption='[[5yew]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5yew]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YEW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YEW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5yew]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YEW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YEW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MFN1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5yew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yew OCA], [http://pdbe.org/5yew PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yew RCSB], [http://www.ebi.ac.uk/pdbsum/5yew PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yew 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=5yew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yew OCA], [https://pdbe.org/5yew PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yew RCSB], [https://www.ebi.ac.uk/pdbsum/5yew PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yew ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MFN1_HUMAN MFN1_HUMAN]] Essential transmembrane GTPase, which mediates mitochondrial fusion. Fusion of mitochondria occurs in many cell types and constitutes an important step in mitochondria morphology, which is balanced between fusion and fission. MFN1 acts independently of the cytoskeleton. Overexpression induces the formation of mitochondrial networks.<ref>PMID:11181170</ref> <ref>PMID:12475957</ref> <ref>PMID:12759376</ref> <ref>PMID:23921378</ref> | + | [https://www.uniprot.org/uniprot/MFN1_HUMAN MFN1_HUMAN] Essential transmembrane GTPase, which mediates mitochondrial fusion. Fusion of mitochondria occurs in many cell types and constitutes an important step in mitochondria morphology, which is balanced between fusion and fission. MFN1 acts independently of the cytoskeleton. Overexpression induces the formation of mitochondrial networks.<ref>PMID:11181170</ref> <ref>PMID:12475957</ref> <ref>PMID:12759376</ref> <ref>PMID:23921378</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Fusion of the outer mitochondrial membrane is mediated by the dynamin-like GTPase mitofusin (MFN). Here, we determined the structure of the minimal GTPase domain (MGD) of human MFN1 in complex with GDP-BeF3(-). The MGD folds into a canonical GTPase fold with an associating four-helix bundle, HB1, and forms a dimer. A potassium ion in the catalytic core engages GDP and BeF3(-) (GDP-BeF3(-)). Enzymatic analysis has confirmed that efficient GTP hydrolysis by MFN1 requires potassium. Compared to previously reported MGD structures, the HB1 structure undergoes a major conformational change relative to the GTPase domains, as they move from pointing in opposite directions to point in the same direction, suggesting that a swing of the four-helix bundle can pull tethered membranes closer to achieve fusion. The proposed model is supported by results from in vitro biochemical assays and mitochondria morphology rescue assays in MFN1-deleted cells. These findings offer an explanation for how Charcot-Marie-Tooth neuropathy type 2 A (CMT2A)-causing mutations compromise MFN-mediated fusion.
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| - | | + | |
| - | Structural basis for GTP hydrolysis and conformational change of MFN1 in mediating membrane fusion.,Yan L, Qi Y, Huang X, Yu C, Lan L, Guo X, Rao Z, Hu J, Lou Z Nat Struct Mol Biol. 2018 Mar;25(3):233-243. doi: 10.1038/s41594-018-0034-8. Epub, 2018 Feb 26. PMID:29483649<ref>PMID:29483649</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5yew" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Huang, X]] | + | [[Category: Large Structures]] |
| - | [[Category: Qi, Y]] | + | [[Category: Huang X]] |
| - | [[Category: Yan, L]] | + | [[Category: Qi Y]] |
| - | [[Category: Yu, C]] | + | [[Category: Yan L]] |
| - | [[Category: Fusion]]
| + | [[Category: Yu C]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Mfn1]]
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| - | [[Category: Mitochondria]]
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| Structural highlights
Function
MFN1_HUMAN Essential transmembrane GTPase, which mediates mitochondrial fusion. Fusion of mitochondria occurs in many cell types and constitutes an important step in mitochondria morphology, which is balanced between fusion and fission. MFN1 acts independently of the cytoskeleton. Overexpression induces the formation of mitochondrial networks.[1] [2] [3] [4]
References
- ↑ Santel A, Fuller MT. Control of mitochondrial morphology by a human mitofusin. J Cell Sci. 2001 Mar;114(Pt 5):867-74. PMID:11181170
- ↑ Legros F, Lombes A, Frachon P, Rojo M. Mitochondrial fusion in human cells is efficient, requires the inner membrane potential, and is mediated by mitofusins. Mol Biol Cell. 2002 Dec;13(12):4343-54. PMID:12475957 doi:http://dx.doi.org/10.1091/mbc.E02-06-0330
- ↑ Santel A, Frank S, Gaume B, Herrler M, Youle RJ, Fuller MT. Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. J Cell Sci. 2003 Jul 1;116(Pt 13):2763-74. Epub 2003 May 20. PMID:12759376 doi:http://dx.doi.org/10.1242/jcs.00479
- ↑ Palmer CS, Elgass KD, Parton RG, Osellame LD, Stojanovski D, Ryan MT. Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission. J Biol Chem. 2013 Sep 20;288(38):27584-93. doi: 10.1074/jbc.M113.479873. Epub, 2013 Aug 6. PMID:23921378 doi:http://dx.doi.org/10.1074/jbc.M113.479873
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