8v8t

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Current revision (11:07, 16 April 2025) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 8v8t is ON HOLD until Paper Publication
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==Asymmetrical subunit from a Drp1 lattice on PA nanotubes==
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<StructureSection load='8v8t' size='340' side='right'caption='[[8v8t]], [[Resolution|resolution]] 14.73&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8v8t]] is a 4 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=8V8T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8V8T FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 14.73&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8v8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8v8t OCA], [https://pdbe.org/8v8t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8v8t RCSB], [https://www.ebi.ac.uk/pdbsum/8v8t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8v8t ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/DNM1L_HUMAN DNM1L_HUMAN] Note=May be associated with Alzheimer disease through beta-amyloid-induced increased S-nitrosylation of DNM1L, which triggers, directly or indirectly, excessive mitochondrial fission, synaptic loss and neuronal damage.<ref>PMID:19342591</ref> Defects in DNM1L are the cause of encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission (EMPF) [MIM:[https://omim.org/entry/614388 614388]. EMPF is a rare autosomal dominant systemic disorder resulting in lack of neurologic development and death in infancy. After birth, infants present in the first week of life with poor feeding and neurologic impairment, including hypotonia, little spontaneous movement, no tendon reflexes, no response to light stimulation, and poor visual fixation. Other features include mildly elevated plasma concentration of very-long-chain fatty acids, lactic acidosis, microcephaly, deep-set eyes, optic atrophy and hypoplasia, and an abnormal gyral pattern in both frontal lobes associated with dysmyelination.<ref>PMID:17460227</ref> <ref>PMID:19342591</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/DNM1L_HUMAN DNM1L_HUMAN] Functions in mitochondrial and peroxisomal division. Mediates membrane fission through oligomerization into ring-like structures which wrap around the scission site to constict and sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism. Required for normal brain development. Facilitates developmentally-regulated apoptosis during neural tube development. Required for a normal rate of cytochrome c release and caspase activation during apoptosis. Also required for mitochondrial fission during mitosis. Required for programmed necrosis execution. May be involved in vesicle transport.<ref>PMID:9570752</ref> <ref>PMID:9786947</ref> <ref>PMID:11514614</ref> <ref>PMID:12499366</ref> <ref>PMID:12618434</ref> <ref>PMID:15208300</ref> <ref>PMID:17015472</ref> <ref>PMID:17301055</ref> <ref>PMID:17553808</ref> <ref>PMID:17460227</ref> <ref>PMID:18695047</ref> <ref>PMID:18838687</ref> <ref>PMID:19638400</ref> <ref>PMID:19411255</ref> <ref>PMID:19342591</ref> <ref>PMID:20688057</ref> Isoform 1 and isoform 4 inhibit peroxisomal division when overexpressed.<ref>PMID:9570752</ref> <ref>PMID:9786947</ref> <ref>PMID:11514614</ref> <ref>PMID:12499366</ref> <ref>PMID:12618434</ref> <ref>PMID:15208300</ref> <ref>PMID:17015472</ref> <ref>PMID:17301055</ref> <ref>PMID:17553808</ref> <ref>PMID:17460227</ref> <ref>PMID:18695047</ref> <ref>PMID:18838687</ref> <ref>PMID:19638400</ref> <ref>PMID:19411255</ref> <ref>PMID:19342591</ref> <ref>PMID:20688057</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Mitochondrial health relies on the membrane fission mediated by dynamin-related protein 1 (Drp1). Previous structural studies of Drp1 on remodeled membranes were hampered by heterogeneity, leaving a critical gap in the understanding of the mitochondrial fission mechanisms. Here we present a cryo-electron microscopy structure of full-length human Drp1 decorated on membrane tubules. Using the reconstruction of average subtracted tubular regions (RASTR) technique, we report that Drp1 forms a locally ordered lattice along the tubule without global helical symmetry. The filaments in the lattice are similar to dynamin rungs with conserved stalk interactions. Adjacent filaments are connected by GTPase domain interactions in a novel stacked conformation. We identified two states of the Drp1 lattice among the heterogenous dataset representing conformational changes around hinge 1. Additionally, we observed contact between Drp1 and membrane that can be assigned to the variable domain sequence. Together these structures revealed a putative mechanism by which Drp1 constricts mitochondria membranes in a stepwise, "ratchet" manner.
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Authors: Rochon, K., Peng, R., Stagg, S.M., Mears, J.A.
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The Structure of the Drp1 Lattice on Membrane.,Peng R, Rochon K, Hutson AN, Stagg SM, Mears JA J Mol Biol. 2025 Apr 2:169125. doi: 10.1016/j.jmb.2025.169125. PMID:40185198<ref>PMID:40185198</ref>
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Description: Asymmetrical subunit from a Drp1 lattice on PA nanotubes
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Mears, J.A]]
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<div class="pdbe-citations 8v8t" style="background-color:#fffaf0;"></div>
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[[Category: Peng, R]]
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== References ==
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[[Category: Stagg, S.M]]
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<references/>
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[[Category: Rochon, K]]
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Hutson AN]]
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[[Category: Mears JA]]
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[[Category: Peng R]]
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[[Category: Rochon K]]
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[[Category: Stagg SM]]

Current revision

Asymmetrical subunit from a Drp1 lattice on PA nanotubes

PDB ID 8v8t

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