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6jfk

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Revision as of 08:43, 27 November 2019

GDP bound Mitofusin2 (MFN2)

Structural highlights

6jfk is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	MFN2, CPRP1, KIAA0214 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MFN2_HUMAN] Multiple symmetric lipomatosis;Autosomal dominant Charcot-Marie-Tooth disease type 2A2;Severe early-onset axonal neuropathy due to MFN2 deficiency;Hereditary motor and sensory neuropathy type 5;Hereditary motor and sensory neuropathy type 6. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

[MFN2_HUMAN] Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:11181170, PubMed:11950885, PubMed:28114303). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events (PubMed:28114303). Overexpression induces the formation of mitochondrial networks (PubMed:28114303). Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains (Probable). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes (By similarity). Plays an important role in the regulation of vascular smooth muscle cell proliferation (By similarity). Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) (PubMed:23620051). Is required for PRKN recruitment to dysfunctional mitochondria (PubMed:23620051). Involved in the control of unfolded protein response (UPR) upon ER stress including activation of apoptosis and autophagy during ER stress (By similarity). Acts as an upstream regulator of EIF2AK3 and suppresses EIF2AK3 activation under basal conditions (By similarity).[UniProtKB:Q80U63][UniProtKB:Q8R500]^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Mitofusin-2 (MFN2) is a dynamin-like GTPase that plays a central role in regulating mitochondrial fusion and cell metabolism. Mutations in MFN2 cause the neurodegenerative disease Charcot-Marie-Tooth type 2A (CMT2A). The molecular basis underlying the physiological and pathological relevance of MFN2 is unclear. Here, we present crystal structures of truncated human MFN2 in different nucleotide-loading states. Unlike other dynamin superfamily members including MFN1, MFN2 forms sustained dimers even after GTP hydrolysis via the GTPase domain (G) interface, which accounts for its high membrane-tethering efficiency. The biochemical discrepancy between human MFN2 and MFN1 largely derives from a primate-only single amino acid variance. MFN2 and MFN1 can form heterodimers via the G interface in a nucleotide-dependent manner. CMT2A-related mutations, mapping to different functional zones of MFN2, lead to changes in GTP hydrolysis and homo/hetero-association ability. Our study provides fundamental insight into how mitofusins mediate mitochondrial fusion and the ways their disruptions cause disease.

Structural insights of human mitofusin-2 into mitochondrial fusion and CMT2A onset.,Li YJ, Cao YL, Feng JX, Qi Y, Meng S, Yang JF, Zhong YT, Kang S, Chen X, Lan L, Luo L, Yu B, Chen S, Chan DC, Hu J, Gao S Nat Commun. 2019 Oct 29;10(1):4914. doi: 10.1038/s41467-019-12912-0. PMID:31664033^[6]

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
↑ Rojo M, Legros F, Chateau D, Lombes A. Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J Cell Sci. 2002 Apr 15;115(Pt 8):1663-74. PMID:11950885
↑ Chen Y, Dorn GW 2nd. PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science. 2013 Apr 26;340(6131):471-5. doi: 10.1126/science.1231031. PMID:23620051 doi:http://dx.doi.org/10.1126/science.1231031
↑ Sawyer SL, Cheuk-Him Ng A, Innes AM, Wagner JD, Dyment DA, Tetreault M, Majewski J, Boycott KM, Screaton RA, Nicholson G. Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy. Hum Mol Genet. 2015 Sep 15;24(18):5109-14. doi: 10.1093/hmg/ddv229. Epub 2015 Jun, 17. PMID:26085578 doi:http://dx.doi.org/10.1093/hmg/ddv229
↑ 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
↑ Li YJ, Cao YL, Feng JX, Qi Y, Meng S, Yang JF, Zhong YT, Kang S, Chen X, Lan L, Luo L, Yu B, Chen S, Chan DC, Hu J, Gao S. Structural insights of human mitofusin-2 into mitochondrial fusion and CMT2A onset. Nat Commun. 2019 Oct 29;10(1):4914. doi: 10.1038/s41467-019-12912-0. PMID:31664033 doi:http://dx.doi.org/10.1038/s41467-019-12912-0

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6jfk"

@@ Line 3: / Line 3: @@
 <StructureSection load='6jfk' size='340' side='right'caption='[[6jfk]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6jfk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JFK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JFK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6jfk]] is a 1 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=6JFK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JFK FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MFN2, CPRP1, KIAA0214 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6jfk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jfk OCA], [http://pdbe.org/6jfk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jfk RCSB], [http://www.ebi.ac.uk/pdbsum/6jfk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jfk ProSAT]</span></td></tr>
 </table>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Cao, Y L]]

6jfk

From Proteopedia

Revision as of 08:43, 27 November 2019

GDP bound Mitofusin2 (MFN2)

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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