4ggd
From Proteopedia
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| - | [[ | + | ==Structural analysis of human Cdc20 supports multisite degron recognition by APC/C.== |
| + | <StructureSection load='4ggd' size='340' side='right' caption='[[4ggd]], [[Resolution|resolution]] 2.44Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4ggd]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GGD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GGD FirstGlance]. <br> | ||
| + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gga|4gga]], [[4ggc|4ggc]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDC20 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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> | ||
| + | <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=4ggd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ggd RCSB], [http://www.ebi.ac.uk/pdbsum/4ggd PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == 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. | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The anaphase-promoting complex/cyclosome (APC/C) promotes anaphase onset and mitotic exit through ubiquitinating securin and cyclin B1. The mitotic APC/C activator, the cell division cycle 20 (Cdc20) protein, directly interacts with APC/C degrons--the destruction (D) and KEN boxes. APC/C(Cdc20) is the target of the spindle checkpoint. Checkpoint inhibition of APC/C(Cdc20) requires the binding of a BubR1 KEN box to Cdc20. How APC/C recognizes substrates is not understood. We report the crystal structures of human Cdc20 alone or bound to a BubR1 KEN box. Cdc20 has a disordered N-terminal region and a C-terminal WD40 beta propeller with a preformed KEN-box-binding site at its top face. We identify a second conserved surface at the side of the Cdc20 beta propeller as a D-box-binding site. The D box of securin, but not its KEN box, is critical for securin ubiquitination by APC/C(Cdc20). Although both motifs contribute to securin ubiquitination by APC/C(Cdh1), securin mutants lacking either motif are efficiently ubiquitinated. Furthermore, D-box peptides diminish the ubiquitination of KEN-box substrates by APC/C(Cdh1), suggesting possible competition between the two motifs. Our results indicate the lack of strong positive cooperativity between the two degrons of securin. We propose that low-cooperativity, multisite target recognition enables APC/C to robustly ubiquitinate diverse substrates and helps to drive cell cycle oscillations. | ||
| - | + | Structural analysis of human Cdc20 supports multisite degron recognition by APC/C.,Tian W, Li B, Warrington R, Tomchick DR, Yu H, Luo X Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18419-24. doi:, 10.1073/pnas.1213438109. Epub 2012 Oct 22. PMID:23091007<ref>PMID:23091007</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| - | + | ==See Also== | |
| - | + | *[[EPSP synthase|EPSP synthase]] | |
| - | == | + | *[[Serine/threonine protein kinase|Serine/threonine protein kinase]] |
| - | [[ | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
| - | [[Category: Luo, X | + | [[Category: Luo, X]] |
| - | [[Category: Tian, W | + | [[Category: Tian, W]] |
| - | [[Category: Tomchick, D R | + | [[Category: Tomchick, D R]] |
[[Category: Cell cycle]] | [[Category: Cell cycle]] | ||
[[Category: Mitosis]] | [[Category: Mitosis]] | ||
Revision as of 17:38, 25 December 2014
Structural analysis of human Cdc20 supports multisite degron recognition by APC/C.
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