5gom

From Proteopedia

(Difference between revisions)

Revision as of 11:38, 2 August 2023

Truncated mitofusin-1, transition-like state

Structural highlights

5gom is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.802Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

Mitochondria are double-membraned organelles with variable shapes influenced by metabolic conditions, developmental stage, and environmental stimuli. Their dynamic morphology is a result of regulated and balanced fusion and fission processes. Fusion is crucial for the health and physiological functions of mitochondria, including complementation of damaged mitochondrial DNAs and the maintenance of membrane potential. Mitofusins are dynamin-related GTPases that are essential for mitochondrial fusion. They are embedded in the mitochondrial outer membrane and thought to fuse adjacent mitochondria via combined oligomerization and GTP hydrolysis. However, the molecular mechanisms of this process remain unknown. Here we present crystal structures of engineered human MFN1 containing the GTPase domain and a helical domain during different stages of GTP hydrolysis. The helical domain is composed of elements from widely dispersed sequence regions of MFN1 and resembles the 'neck' of the bacterial dynamin-like protein. The structures reveal unique features of its catalytic machinery and explain how GTP binding induces conformational changes to promote GTPase domain dimerization in the transition state. Disruption of GTPase domain dimerization abolishes the fusogenic activity of MFN1. Moreover, a conserved aspartate residue trigger was found to affect mitochondrial elongation in MFN1, probably through a GTP-loading-dependent domain rearrangement. Thus, we propose a mechanistic model for MFN1-mediated mitochondrial tethering, and our results shed light on the molecular basis of mitochondrial fusion and mitofusin-related human neuromuscular disorders.

MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion.,Cao YL, Meng S, Chen Y, Feng JX, Gu DD, Yu B, Li YJ, Yang JY, Liao S, Chan DC, Gao S Nature. 2017 Feb 16;542(7641):372-376. doi: 10.1038/nature21077. Epub 2017 Jan, 23. PMID:28114303^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Cao YL, Meng S, Chen Y, Feng JX, Gu DD, Yu B, Li YJ, Yang JY, Liao S, Chan DC, Gao S. MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion. Nature. 2017 Feb 16;542(7641):372-376. doi: 10.1038/nature21077. Epub 2017 Jan, 23. PMID:28114303 doi:http://dx.doi.org/10.1038/nature21077

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5gom"

Categories: Homo sapiens | Large Structures | Cao YL | Gao S

@@ Line 3: / Line 3: @@
 <StructureSection load='5gom' size='340' side='right'caption='[[5gom]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5gom]] is a 2 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=5GOM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5GOM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5gom]] is a 2 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=5GOM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GOM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</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]] 2.802&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5gof|5gof]], [[5goe|5goe]], [[5go4|5go4]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5gom FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gom OCA], [https://pdbe.org/5gom PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gom RCSB], [https://www.ebi.ac.uk/pdbsum/5gom PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gom ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5gom FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gom OCA], [http://pdbe.org/5gom PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gom RCSB], [http://www.ebi.ac.uk/pdbsum/5gom PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gom ProSAT]</span></td></tr>
 </table>
 == 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 ==
@@ Line 24: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Cao, Y L]]
+[[Category: Cao YL]]
-[[Category: Gao, S]]
+[[Category: Gao S]]
-[[Category: Hydrolase]]
-[[Category: Mitochondrial fusion]]

5gom

From Proteopedia

Revision as of 11:38, 2 August 2023

Truncated mitofusin-1, transition-like state

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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