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- | [[Image:3b9p.jpg|left|200px]] | |
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- | <!--
| + | ==Spastin== |
- | The line below this paragraph, containing "STRUCTURE_3b9p", creates the "Structure Box" on the page.
| + | <StructureSection load='3b9p' size='340' side='right'caption='[[3b9p]], [[Resolution|resolution]] 2.70Å' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[3b9p]] is a 1 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=3B9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3B9P FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
- | -->
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
- | {{STRUCTURE_3b9p| PDB=3b9p | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3b9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b9p OCA], [https://pdbe.org/3b9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3b9p RCSB], [https://www.ebi.ac.uk/pdbsum/3b9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3b9p ProSAT]</span></td></tr> |
- | | + | </table> |
- | '''Spastin''' | + | == Function == |
- | | + | [https://www.uniprot.org/uniprot/SPAST_DROME SPAST_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.<ref>PMID:15242610</ref> <ref>PMID:15562320</ref> <ref>PMID:15823537</ref> <ref>PMID:16276413</ref> <ref>PMID:17452528</ref> <ref>PMID:19341724</ref> <ref>PMID:18202664</ref> |
- | | + | == Evolutionary Conservation == |
- | ==Overview== | + | [[Image:Consurf_key_small.gif|200px|right]] |
- | Spastin, the most common locus for mutations in hereditary spastic paraplegias, and katanin are related microtubule-severing AAA ATPases involved in constructing neuronal and non-centrosomal microtubule arrays and in segregating chromosomes. The mechanism by which spastin and katanin break and destabilize microtubules is unknown, in part owing to the lack of structural information on these enzymes. Here we report the X-ray crystal structure of the Drosophila spastin AAA domain and provide a model for the active spastin hexamer generated using small-angle X-ray scattering combined with atomic docking. The spastin hexamer forms a ring with a prominent central pore and six radiating arms that may dock onto the microtubule. Helices unique to the microtubule-severing AAA ATPases surround the entrances to the pore on either side of the ring, and three highly conserved loops line the pore lumen. Mutagenesis reveals essential roles for these structural elements in the severing reaction. Peptide and antibody inhibition experiments further show that spastin may dismantle microtubules by recognizing specific features in the carboxy-terminal tail of tubulin. Collectively, our data support a model in which spastin pulls the C terminus of tubulin through its central pore, generating a mechanical force that destabilizes tubulin-tubulin interactions within the microtubule lattice. Our work also provides insights into the structural defects in spastin that arise from mutations identified in hereditary spastic paraplegia patients.
| + | Check<jmol> |
- | | + | <jmolCheckbox> |
- | ==About this Structure== | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b9/3b9p_consurf.spt"</scriptWhenChecked> |
- | 3B9P is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B9P OCA].
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
- | | + | <text>to colour the structure by Evolutionary Conservation</text> |
- | ==Reference== | + | </jmolCheckbox> |
- | Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin., Roll-Mecak A, Vale RD, Nature. 2008 Jan 17;451(7176):363-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18202664 18202664]
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3b9p ConSurf]. |
| + | <div style="clear:both"></div> |
| + | == References == |
| + | <references/> |
| + | __TOC__ |
| + | </StructureSection> |
| [[Category: Drosophila melanogaster]] | | [[Category: Drosophila melanogaster]] |
- | [[Category: Single protein]] | + | [[Category: Large Structures]] |
- | [[Category: Roll-Mecak, A.]] | + | [[Category: Roll-Mecak A]] |
- | [[Category: Vale, R D.]] | + | [[Category: Vale RD]] |
- | [[Category: Aaa atpase]]
| + | |
- | [[Category: Atp-binding]]
| + | |
- | [[Category: Hydrolase]]
| + | |
- | [[Category: Nucleotide-binding]]
| + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 20:33:21 2008''
| + | |
| Structural highlights
Function
SPAST_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.[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Trotta N, Orso G, Rossetto MG, Daga A, Broadie K. The hereditary spastic paraplegia gene, spastin, regulates microtubule stability to modulate synaptic structure and function. Curr Biol. 2004 Jul 13;14(13):1135-47. PMID:15242610 doi:http://dx.doi.org/10.1016/j.cub.2004.06.058
- ↑ Sherwood NT, Sun Q, Xue M, Zhang B, Zinn K. Drosophila spastin regulates synaptic microtubule networks and is required for normal motor function. PLoS Biol. 2004 Dec;2(12):e429. Epub 2004 Nov 30. PMID:15562320 doi:http://dx.doi.org/10.1371/journal.pbio.0020429
- ↑ Roll-Mecak A, Vale RD. The Drosophila homologue of the hereditary spastic paraplegia protein, spastin, severs and disassembles microtubules. Curr Biol. 2005 Apr 12;15(7):650-5. PMID:15823537 doi:http://dx.doi.org/S0960-9822(05)00170-3
- ↑ Orso G, Martinuzzi A, Rossetto MG, Sartori E, Feany M, Daga A. Disease-related phenotypes in a Drosophila model of hereditary spastic paraplegia are ameliorated by treatment with vinblastine. J Clin Invest. 2005 Nov;115(11):3026-34. PMID:16276413 doi:http://dx.doi.org/10.1172/JCI24694
- ↑ Zhang D, Rogers GC, Buster DW, Sharp DJ. Three microtubule severing enzymes contribute to the "Pacman-flux" machinery that moves chromosomes. J Cell Biol. 2007 Apr 23;177(2):231-42. PMID:17452528 doi:http://dx.doi.org/jcb.200612011
- ↑ Lee M, Paik SK, Lee MJ, Kim YJ, Kim S, Nahm M, Oh SJ, Kim HM, Yim J, Lee CJ, Bae YC, Lee S. Drosophila Atlastin regulates the stability of muscle microtubules and is required for synapse development. Dev Biol. 2009 Jun 15;330(2):250-62. doi: 10.1016/j.ydbio.2009.03.019. Epub 2009 , Mar 31. PMID:19341724 doi:http://dx.doi.org/10.1016/j.ydbio.2009.03.019
- ↑ Roll-Mecak A, Vale RD. Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin. Nature. 2008 Jan 17;451(7176):363-7. PMID:18202664 doi:10.1038/nature06482
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