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| | <StructureSection load='1t5c' size='340' side='right'caption='[[1t5c]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='1t5c' size='340' side='right'caption='[[1t5c]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1t5c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T5C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1t5c]] is a 2 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=1T5C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T5C FirstGlance]. <br> |
| - | </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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PIN:PIPERAZINE-N,N-BIS(2-ETHANESULFONIC+ACID)'>PIN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CENPE ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PIN:PIPERAZINE-N,N-BIS(2-ETHANESULFONIC+ACID)'>PIN</scene></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=1t5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5c OCA], [https://pdbe.org/1t5c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t5c RCSB], [https://www.ebi.ac.uk/pdbsum/1t5c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t5c ProSAT]</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=1t5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5c OCA], [https://pdbe.org/1t5c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t5c RCSB], [https://www.ebi.ac.uk/pdbsum/1t5c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t5c ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CENPE_HUMAN CENPE_HUMAN]] Essential for the maintenance of chromosomal stability through efficient stabilization of microtubule capture at kinetochores. Plays a key role in the movement of chromosomes toward the metaphase plate during mitosis. Is a slow plus end-directed motor whose activity is essential for metaphase chromosome alignment. Couples chromosome position to microtubule depolymerizing activity. The highly processive microtubule-dependent motor activity of CENPE serves to power chromosome congression and provides a flexible, motile tether linking kinetochores to dynamic spindle microtubules. Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss. Required for the efficient recruitment of BUBR1, MAD1 and MAD2 to attached and newly unattached kinetochores. Stimulates mammalian BUBR1 kinase activity. Accumulates just before mitosis at the G2 phase of the cell cycle.<ref>PMID:7889940</ref> <ref>PMID:17535814</ref>
| + | [https://www.uniprot.org/uniprot/CENPE_HUMAN CENPE_HUMAN] Essential for the maintenance of chromosomal stability through efficient stabilization of microtubule capture at kinetochores. Plays a key role in the movement of chromosomes toward the metaphase plate during mitosis. Is a slow plus end-directed motor whose activity is essential for metaphase chromosome alignment. Couples chromosome position to microtubule depolymerizing activity. The highly processive microtubule-dependent motor activity of CENPE serves to power chromosome congression and provides a flexible, motile tether linking kinetochores to dynamic spindle microtubules. Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss. Required for the efficient recruitment of BUBR1, MAD1 and MAD2 to attached and newly unattached kinetochores. Stimulates mammalian BUBR1 kinase activity. Accumulates just before mitosis at the G2 phase of the cell cycle.<ref>PMID:7889940</ref> <ref>PMID:17535814</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Garcia-Saez, I]] | + | [[Category: Garcia-Saez I]] |
| - | [[Category: Kozielski, F]] | + | [[Category: Kozielski F]] |
| - | [[Category: SPINE, Structural Proteomics in Europe]]
| + | [[Category: Wade RH]] |
| - | [[Category: Wade, R H]] | + | [[Category: Yen T]] |
| - | [[Category: Yen, T]] | + | |
| - | [[Category: Arrow-head shape]]
| + | |
| - | [[Category: Contractile protein]]
| + | |
| - | [[Category: Kinesin motor-domain-adp complex]]
| + | |
| - | [[Category: Spine]]
| + | |
| - | [[Category: Stranded beta-sheet core with solvent exposed alpha-helice]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| - | [[Category: Structural proteomics in europe]]
| + | |
| Structural highlights
Function
CENPE_HUMAN Essential for the maintenance of chromosomal stability through efficient stabilization of microtubule capture at kinetochores. Plays a key role in the movement of chromosomes toward the metaphase plate during mitosis. Is a slow plus end-directed motor whose activity is essential for metaphase chromosome alignment. Couples chromosome position to microtubule depolymerizing activity. The highly processive microtubule-dependent motor activity of CENPE serves to power chromosome congression and provides a flexible, motile tether linking kinetochores to dynamic spindle microtubules. Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss. Required for the efficient recruitment of BUBR1, MAD1 and MAD2 to attached and newly unattached kinetochores. Stimulates mammalian BUBR1 kinase activity. Accumulates just before mitosis at the G2 phase of the cell cycle.[1] [2]
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
The human kinetochore is a highly complex macromolecular structure that connects chromosomes to spindle microtubules (MTs) in order to facilitate accurate chromosome segregation. Centromere-associated protein E (CENP-E), a member of the kinesin superfamily, is an essential component of the kinetochore, since it is required to stabilize the attachment of chromosomes to spindle MTs, to develop tension across aligned chromosomes, to stabilize spindle poles and to satisfy the mitotic checkpoint. Here we report the 2.5A resolution crystal structure of the motor domain and linker region of human CENP-E with MgADP bound in the active site. This structure displays subtle but important differences compared to the structures of human Eg5 and conventional kinesin. Our structure reveals that the CENP-E linker region is in a "docked" position identical to that in the human plus-end directed conventional kinesin. CENP-E has many advantages as a potential anti-mitotic drug target and this crystal structure of human CENP-E will provide a starting point for high throughput virtual screening of potential inhibitors.
Crystal structure of the motor domain of the human kinetochore protein CENP-E.,Garcia-Saez I, Yen T, Wade RH, Kozielski F J Mol Biol. 2004 Jul 23;340(5):1107-16. PMID:15236970[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Thrower DA, Jordan MA, Schaar BT, Yen TJ, Wilson L. Mitotic HeLa cells contain a CENP-E-associated minus end-directed microtubule motor. EMBO J. 1995 Mar 1;14(5):918-26. PMID:7889940
- ↑ Liu D, Ding X, Du J, Cai X, Huang Y, Ward T, Shaw A, Yang Y, Hu R, Jin C, Yao X. Human NUF2 interacts with centromere-associated protein E and is essential for a stable spindle microtubule-kinetochore attachment. J Biol Chem. 2007 Jul 20;282(29):21415-24. Epub 2007 May 29. PMID:17535814 doi:http://dx.doi.org/10.1074/jbc.M609026200
- ↑ Garcia-Saez I, Yen T, Wade RH, Kozielski F. Crystal structure of the motor domain of the human kinetochore protein CENP-E. J Mol Biol. 2004 Jul 23;340(5):1107-16. PMID:15236970 doi:http://dx.doi.org/10.1016/j.jmb.2004.05.053
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