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| - | ==CRYSTAL STRUCTURE OF A BONSAI VERSION OF THE HUMAN NDC80 COMPLEX== | + | |
| - | <StructureSection load='2ve7' size='340' side='right' caption='[[2ve7]], [[Resolution|resolution]] 2.88Å' scene=''> | + | ==Crystal structure of a bonsai version of the human Ndc80 complex== |
| | + | <StructureSection load='2ve7' size='340' side='right'caption='[[2ve7]], [[Resolution|resolution]] 2.88Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ve7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VE7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VE7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ve7]] 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=2VE7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VE7 FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPH:PHENOL'>IPH</scene><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]] 2.88Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ve7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ve7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ve7 RCSB], [http://www.ebi.ac.uk/pdbsum/2ve7 PDBsum]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPH:PHENOL'>IPH</scene></td></tr> |
| - | <table> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ve7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ve7 OCA], [https://pdbe.org/2ve7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ve7 RCSB], [https://www.ebi.ac.uk/pdbsum/2ve7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ve7 ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SPC25_HUMAN SPC25_HUMAN] Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:14699129, PubMed:14738735). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:14699129, PubMed:14738735). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020).<ref>PMID:14699129</ref> <ref>PMID:14738735</ref> <ref>PMID:23085020</ref> [https://www.uniprot.org/uniprot/NDC80_HUMAN NDC80_HUMAN] Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore.<ref>PMID:9315664</ref> <ref>PMID:12351790</ref> <ref>PMID:14654001</ref> <ref>PMID:15235793</ref> <ref>PMID:15062103</ref> <ref>PMID:15239953</ref> <ref>PMID:14699129</ref> <ref>PMID:15548592</ref> <ref>PMID:16732327</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ve/2ve7_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ve/2ve7_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </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=2ve7 ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2ve7" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Ciferri, C.]] | + | [[Category: Large Structures]] |
| - | [[Category: Luca, J G.De.]] | + | [[Category: Ciferri C]] |
| - | [[Category: Maiolica, A.]]
| + | [[Category: De Luca JG]] |
| - | [[Category: Moores, C A.]]
| + | [[Category: De Wulf P]] |
| - | [[Category: Musacchio, A.]] | + | [[Category: Dos Reis G]] |
| - | [[Category: Pasqualato, S.]] | + | [[Category: Maiolica A]] |
| - | [[Category: Polka, J.]]
| + | [[Category: Moores CA]] |
| - | [[Category: Rappsilber, J.]]
| + | [[Category: Musacchio A]] |
| - | [[Category: Reis, G Dos.]] | + | [[Category: Pasqualato S]] |
| - | [[Category: Salek, M.]] | + | [[Category: Polka J]] |
| - | [[Category: Salmon, E D.]] | + | [[Category: Rappsilber J]] |
| - | [[Category: Screpanti, E.]] | + | [[Category: Salek M]] |
| - | [[Category: Wulf, P De.]] | + | [[Category: Salmon ED]] |
| - | [[Category: Calponin homology]] | + | [[Category: Screpanti E]] |
| - | [[Category: Cell cycle]] | + | |
| - | [[Category: Cell division]] | + | |
| - | [[Category: Centromere]] | + | |
| - | [[Category: Kinetochore]] | + | |
| - | [[Category: Microtubule]]
| + | |
| - | [[Category: Mitosis]]
| + | |
| Structural highlights
Function
SPC25_HUMAN Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:14699129, PubMed:14738735). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:14699129, PubMed:14738735). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020).[1] [2] [3] NDC80_HUMAN Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore.[4] [5] [6] [7] [8] [9] [10] [11] [12]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Kinetochores are proteinaceous assemblies that mediate the interaction of chromosomes with the mitotic spindle. The 180 kDa Ndc80 complex is a direct point of contact between kinetochores and microtubules. Its four subunits contain coiled coils and form an elongated rod structure with functional globular domains at either end. We crystallized an engineered "bonsai" Ndc80 complex containing a shortened rod domain but retaining the globular domains required for kinetochore localization and microtubule binding. The structure reveals a microtubule-binding interface containing a pair of tightly interacting calponin-homology (CH) domains with a previously unknown arrangement. The interaction with microtubules is cooperative and predominantly electrostatic. It involves positive charges in the CH domains and in the N-terminal tail of the Ndc80 subunit and negative charges in tubulin C-terminal tails and is regulated by the Aurora B kinase. We discuss our results with reference to current models of kinetochore-microtubule attachment and centromere organization.
Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex.,Ciferri C, Pasqualato S, Screpanti E, Varetti G, Santaguida S, Dos Reis G, Maiolica A, Polka J, De Luca JG, De Wulf P, Salek M, Rappsilber J, Moores CA, Salmon ED, Musacchio A Cell. 2008 May 2;133(3):427-39. PMID:18455984[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bharadwaj R, Qi W, Yu H. Identification of two novel components of the human NDC80 kinetochore complex. J Biol Chem. 2004 Mar 26;279(13):13076-85. Epub 2003 Dec 29. PMID:14699129 doi:http://dx.doi.org/10.1074/jbc.M310224200
- ↑ McCleland ML, Kallio MJ, Barrett-Wilt GA, Kestner CA, Shabanowitz J, Hunt DF, Gorbsky GJ, Stukenberg PT. The vertebrate Ndc80 complex contains Spc24 and Spc25 homologs, which are required to establish and maintain kinetochore-microtubule attachment. Curr Biol. 2004 Jan 20;14(2):131-7. PMID:14738735 doi:10.1016/j.cub.2003.12.058
- ↑ Schmidt JC, Arthanari H, Boeszoermenyi A, Dashkevich NM, Wilson-Kubalek EM, Monnier N, Markus M, Oberer M, Milligan RA, Bathe M, Wagner G, Grishchuk EL, Cheeseman IM. The Kinetochore-Bound Ska1 Complex Tracks Depolymerizing Microtubules and Binds to Curved Protofilaments. Dev Cell. 2012 Oct 17. pii: S1534-5807(12)00423-6. doi:, 10.1016/j.devcel.2012.09.012. PMID:23085020 doi:http://dx.doi.org/10.1016/j.devcel.2012.09.012
- ↑ Chen Y, Riley DJ, Chen PL, Lee WH. HEC, a novel nuclear protein rich in leucine heptad repeats specifically involved in mitosis. Mol Cell Biol. 1997 Oct;17(10):6049-56. PMID:9315664
- ↑ Martin-Lluesma S, Stucke VM, Nigg EA. Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2. Science. 2002 Sep 27;297(5590):2267-70. PMID:12351790 doi:http://dx.doi.org/10.1126/science.1075596
- ↑ DeLuca JG, Howell BJ, Canman JC, Hickey JM, Fang G, Salmon ED. Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 and Mad2 to kinetochores. Curr Biol. 2003 Dec 2;13(23):2103-9. PMID:14654001
- ↑ Stucke VM, Baumann C, Nigg EA. Kinetochore localization and microtubule interaction of the human spindle checkpoint kinase Mps1. Chromosoma. 2004 Aug;113(1):1-15. Epub 2004 Jul 3. PMID:15235793 doi:http://dx.doi.org/10.1007/s00412-004-0288-2
- ↑ Joseph J, Liu ST, Jablonski SA, Yen TJ, Dasso M. The RanGAP1-RanBP2 complex is essential for microtubule-kinetochore interactions in vivo. Curr Biol. 2004 Apr 6;14(7):611-7. PMID:15062103 doi:http://dx.doi.org/10.1016/j.cub.2004.03.031
- ↑ Meraldi P, Draviam VM, Sorger PK. Timing and checkpoints in the regulation of mitotic progression. Dev Cell. 2004 Jul;7(1):45-60. PMID:15239953 doi:http://dx.doi.org/10.1016/j.devcel.2004.06.006
- ↑ Bharadwaj R, Qi W, Yu H. Identification of two novel components of the human NDC80 kinetochore complex. J Biol Chem. 2004 Mar 26;279(13):13076-85. Epub 2003 Dec 29. PMID:14699129 doi:http://dx.doi.org/10.1074/jbc.M310224200
- ↑ DeLuca JG, Dong Y, Hergert P, Strauss J, Hickey JM, Salmon ED, McEwen BF. Hec1 and nuf2 are core components of the kinetochore outer plate essential for organizing microtubule attachment sites. Mol Biol Cell. 2005 Feb;16(2):519-31. Epub 2004 Nov 17. PMID:15548592 doi:http://dx.doi.org/10.1091/mbc.E04-09-0852
- ↑ Lin YT, Chen Y, Wu G, Lee WH. Hec1 sequentially recruits Zwint-1 and ZW10 to kinetochores for faithful chromosome segregation and spindle checkpoint control. Oncogene. 2006 Nov 2;25(52):6901-14. Epub 2006 May 29. PMID:16732327 doi:http://dx.doi.org/1209687
- ↑ Ciferri C, Pasqualato S, Screpanti E, Varetti G, Santaguida S, Dos Reis G, Maiolica A, Polka J, De Luca JG, De Wulf P, Salek M, Rappsilber J, Moores CA, Salmon ED, Musacchio A. Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex. Cell. 2008 May 2;133(3):427-39. PMID:18455984 doi:http://dx.doi.org/S0092-8674(08)00401-7
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