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| ==Spastin hexamer in complex with substrate== | | ==Spastin hexamer in complex with substrate== |
| <StructureSection load='6p07' size='340' side='right'caption='[[6p07]], [[Resolution|resolution]] 3.20Å' scene=''> | | <SX load='6p07' size='340' side='right' viewer='molstar' caption='[[6p07]], [[Resolution|resolution]] 3.20Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6p07]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P07 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P07 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6p07]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P07 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P07 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</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">Electron Microscopy, [[Resolution|Resolution]] 3.2Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">spas, D-spastin, Dmel\CG5977, Dspastin, Spas, Spastin, CG5977, Dmel_CG5977 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Microtubule-severing_ATPase Microtubule-severing ATPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.6.1.1 5.6.1.1] </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=6p07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p07 OCA], [https://pdbe.org/6p07 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p07 RCSB], [https://www.ebi.ac.uk/pdbsum/6p07 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p07 ProSAT]</span></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=6p07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p07 OCA], [http://pdbe.org/6p07 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p07 RCSB], [http://www.ebi.ac.uk/pdbsum/6p07 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p07 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/A0A126GV13_DROME A0A126GV13_DROME]] ATP-dependent microtubule severing protein. Stimulates microtubule minus-end depolymerization and poleward microtubule flux in the mitotic spindle. Regulates microtubule stability in the neuromuscular junction synapse. Involved in lipid metabolism by regulating the size and distribution of lipid droplets. Involved in axon regeneration by regulating microtubule severing.[HAMAP-Rule:MF_03021] | | [https://www.uniprot.org/uniprot/A0A0B4LHJ5_DROME A0A0B4LHJ5_DROME] ATP-dependent microtubule severing protein. Stimulates microtubule minus-end depolymerization and poleward microtubule flux in the mitotic spindle. Regulates microtubule stability in the neuromuscular junction synapse. Involved in lipid metabolism by regulating the size and distribution of lipid droplets. Involved in axon regeneration by regulating microtubule severing.[HAMAP-Rule:MF_03021] |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The AAA+ ATPase spastin remodels microtubule arrays through severing and its mutation is the most common cause of hereditary spastic paraplegias (HSP). Polyglutamylation of the tubulin C-terminal tail recruits spastin to microtubules and modulates severing activity. Here, we present a ~3.2 A resolution cryo-EM structure of the Drosophila melanogaster spastin hexamer with a polyglutamate peptide bound in its central pore. Two electropositive loops arranged in a double-helical staircase coordinate the substrate sidechains. The structure reveals how concurrent nucleotide and substrate binding organizes the conserved spastin pore loops into an ordered network that is allosterically coupled to oligomerization, and suggests how tubulin tail engagement activates spastin for microtubule disassembly. This allosteric coupling may apply generally in organizing AAA+ protein translocases into their active conformations. We show that this allosteric network is essential for severing and is a hotspot for HSP mutations.
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| An allosteric network in spastin couples multiple activities required for microtubule severing.,Sandate CR, Szyk A, Zehr EA, Lander GC, Roll-Mecak A Nat Struct Mol Biol. 2019 Jul 8. pii: 10.1038/s41594-019-0257-3. doi:, 10.1038/s41594-019-0257-3. PMID:31285604<ref>PMID:31285604</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 6p07" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </SX> |
| [[Category: Drome]] | | [[Category: Drosophila melanogaster]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Microtubule-severing ATPase]]
| | [[Category: Lander GC]] |
| [[Category: Lander, G C]] | | [[Category: Roll-Mecak A]] |
| [[Category: Roll-Mecak, A]] | | [[Category: Sandate CR]] |
| [[Category: Sandate, C R]] | | [[Category: Szyk A]] |
| [[Category: Szyk, A]] | | [[Category: Zehr E]] |
| [[Category: Zehr, E]] | |
| [[Category: Aaa+ atpase]]
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| [[Category: Homohexamer]]
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| [[Category: Microtubule severing enzyme]]
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| [[Category: Motor protein]]
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