View source for 4bej


==Nucleotide-free Dynamin 1-like protein (DNM1L, DRP1, DLP1)==
<StructureSection load='4bej' size='340' side='right'caption='[[4bej]], [[Resolution|resolution]] 3.48&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4bej]] 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=4BEJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BEJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.483&#8491;</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=4bej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bej OCA], [https://pdbe.org/4bej PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bej RCSB], [https://www.ebi.ac.uk/pdbsum/4bej PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bej ProSAT]</span></td></tr>
</table>
== Disease ==
[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> 
== Function ==
[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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== Publication Abstract from PubMed ==
Dynamin 1-like protein (DNM1L) mediates fission of mitochondria and peroxisomes, and dysfunction of DNM1L has been implicated in several neurological disorders. To study the molecular basis of mitochondrial remodelling, we determined the crystal structure of DNM1L that is comprised of a G domain, a bundle signalling element and a stalk. DNM1L assembled via a central stalk interface, and mutations in this interface disrupted dimerization and interfered with membrane binding and mitochondrial targeting. Two sequence stretches at the tip of the stalk were shown to be required for ordered assembly of DNM1L on membranes and its function in mitochondrial fission. In the crystals, DNM1L dimers further assembled via a second, previously undescribed, stalk interface to form a linear filament. Mutations in this interface interfered with liposome tubulation and mitochondrial remodelling. Based on these results and electron microscopy reconstructions, we propose an oligomerization mode for DNM1L which differs from that of dynamin and might be adapted to the remodelling of mitochondria.

Structural insights into oligomerization and mitochondrial remodelling of dynamin 1-like protein.,Frohlich C, Grabiger S, Schwefel D, Faelber K, Rosenbaum E, Mears J, Rocks O, Daumke O EMBO J. 2013 May 2;32(9):1280-92. doi: 10.1038/emboj.2013.74. Epub 2013 Apr 12. PMID:23584531<ref>PMID:23584531</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4bej" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Daumke O]]
[[Category: Faelber K]]
[[Category: Froehlich C]]
[[Category: Schwefel D]]