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| ==Kinetochore-BUBR1 kinase complex== | | ==Kinetochore-BUBR1 kinase complex== |
| <StructureSection load='3si5' size='340' side='right' caption='[[3si5]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='3si5' size='340' side='right'caption='[[3si5]], [[Resolution|resolution]] 2.20Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3si5]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SI5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SI5 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3si5]] 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=3SI5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SI5 FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wvi|2wvi]], [[3esl|3esl]], [[2lah|2lah]], [[3e7e|3e7e]], [[2i3s|2i3s]]</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]] 2.2Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BUB1B, BUBR1, MAD3L, SSK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CASC5, KIAA1570, KNL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3si5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3si5 OCA], [https://pdbe.org/3si5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3si5 RCSB], [https://www.ebi.ac.uk/pdbsum/3si5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3si5 ProSAT]</span></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
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| <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=3si5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3si5 OCA], [http://pdbe.org/3si5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3si5 RCSB], [http://www.ebi.ac.uk/pdbsum/3si5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3si5 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Disease == | | == Disease == |
| [[http://www.uniprot.org/uniprot/BUB1B_HUMAN BUB1B_HUMAN]] Mosaic variegated aneuploidy syndrome. Defects in BUB1B are associated with tumor formation. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. MVA1 is caused by biallelic mutations in the BUB1B gene. [[http://www.uniprot.org/uniprot/CASC5_HUMAN CASC5_HUMAN]] Autosomal recessive primary microcephaly. A chromosomal aberration involving CASC5 is associated with acute myeloblastic leukemia (AML). Translocation t(11;15)(q23;q14) with KMT2A/MLL1. May give rise to a KMT2A/MLL1-CASC5 fusion protein. The disease is caused by mutations affecting the gene represented in this entry. | | [https://www.uniprot.org/uniprot/BUB1B_HUMAN BUB1B_HUMAN] Mosaic variegated aneuploidy syndrome. Defects in BUB1B are associated with tumor formation. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. MVA1 is caused by biallelic mutations in the BUB1B gene. |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/BUB1B_HUMAN BUB1B_HUMAN]] Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression.<ref>PMID:10477750</ref> <ref>PMID:11702782</ref> <ref>PMID:14706340</ref> <ref>PMID:15020684</ref> <ref>PMID:19411850</ref> <ref>PMID:19503101</ref> [[http://www.uniprot.org/uniprot/CASC5_HUMAN CASC5_HUMAN]] Performs two crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Required for attachment of the kinetochores to the spindle microtubules. Directly links BUB1 and BUB1B to kinetochores. Part of the MIS12 complex, which may be fundamental for kinetochore formation and proper chromosome segregation during mitosis. Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore.<ref>PMID:15502821</ref> <ref>PMID:17981135</ref> <ref>PMID:18045986</ref> | | [https://www.uniprot.org/uniprot/BUB1B_HUMAN BUB1B_HUMAN] Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression.<ref>PMID:10477750</ref> <ref>PMID:11702782</ref> <ref>PMID:14706340</ref> <ref>PMID:15020684</ref> <ref>PMID:19411850</ref> <ref>PMID:19503101</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The maintenance of genomic stability relies on the spindle assembly checkpoint (SAC), which ensures accurate chromosome segregation by delaying the onset of anaphase until all chromosomes are properly bioriented and attached to the mitotic spindle. BUB1 and BUBR1 kinases are central for this process and by interacting with Blinkin, link the SAC with the kinetochore, the macromolecular assembly that connects microtubules with centromeric DNA. Here, we identify the Blinkin motif critical for interaction with BUBR1, define the stoichiometry and affinity of the interaction, and present a 2.2 A resolution crystal structure of the complex. The structure defines an unanticipated BUBR1 region responsible for the interaction and reveals a novel Blinkin motif that undergoes a disorder-to-order transition upon ligand binding. We also show that substitution of several BUBR1 residues engaged in binding Blinkin leads to defects in the SAC, thus providing the first molecular details of the recognition mechanism underlying kinetochore-SAC signaling.
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| Structure of a Blinkin-BUBR1 Complex Reveals an Interaction Crucial for Kinetochore-Mitotic Checkpoint Regulation via an Unanticipated Binding Site.,Bolanos-Garcia VM, Lischetti T, Matak-Vinkovic D, Cota E, Simpson PJ, Chirgadze DY, Spring DR, Robinson CV, Nilsson J, Blundell TL Structure. 2011 Oct 12. PMID:22000412<ref>PMID:22000412</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 3si5" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Serine/threonine protein kinase|Serine/threonine protein kinase]] | | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Non-specific serine/threonine protein kinase]] | | [[Category: Large Structures]] |
| [[Category: Blundell, T L]] | | [[Category: Blundell TL]] |
| [[Category: Bolanos-Garcia, V M]] | | [[Category: Bolanos-Garcia VM]] |
| [[Category: Chirgadze, D Y]] | | [[Category: Chirgadze DY]] |
| [[Category: Blinkin/knl1]]
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| [[Category: Bubr1]]
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| [[Category: Bubr1-blinkin complex]]
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| [[Category: Cell cycle]]
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| [[Category: Chromosome segregation]]
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| [[Category: Mitotic checkpoint]]
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