1t5c

From Proteopedia

(Difference between revisions)

Revision as of 13:51, 25 December 2014

Crystal structure of the motor domain of human kinetochore protein CENP-E

Structural highlights

1t5c is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Gene:	CENPE (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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.

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1t5c"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1t5c]] is a 2 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=1T5C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T5C FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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><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=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><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CENPE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CENPE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=1t5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t5c RCSB], [http://www.ebi.ac.uk/pdbsum/1t5c PDBsum]</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=1t5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t5c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t5c RCSB], [http://www.ebi.ac.uk/pdbsum/1t5c PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 35: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Garcia-Saez, I.]]
+[[Category: Garcia-Saez, I]]
-[[Category: Kozielski, F.]]
+[[Category: Kozielski, F]]
-[[Category: SPINE, Structural Proteomics in Europe.]]
+[[Category: SPINE, Structural Proteomics in Europe]]
-[[Category: Wade, R H.]]
+[[Category: Wade, R H]]
-[[Category: Yen, T.]]
+[[Category: Yen, T]]
 [[Category: Arrow-head shape]]
 [[Category: Contractile protein]]

1t5c

From Proteopedia

Revision as of 13:51, 25 December 2014

Crystal structure of the motor domain of human kinetochore protein CENP-E

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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