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| | ==Structural analysis of human Cdc20 supports multisite degron recognition by APC/C.== | | ==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=''> | + | <StructureSection load='4ggd' size='340' side='right'caption='[[4ggd]], [[Resolution|resolution]] 2.44Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ggd]] 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=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> | + | <table><tr><td colspan='2'>[[4ggd]] 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=4GGD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/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> | + | </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=4ggd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggd OCA], [https://pdbe.org/4ggd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ggd RCSB], [https://www.ebi.ac.uk/pdbsum/4ggd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ggd ProSAT]</span></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 HUMAN])</td></tr>
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| - | <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=4ggd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggd OCA], [http://pdbe.org/4ggd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ggd RCSB], [http://www.ebi.ac.uk/pdbsum/4ggd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ggd ProSAT]</span></td></tr> | + | |
| | </table> | | </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 == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CDC20_HUMAN CDC20_HUMAN]] Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation.<ref>PMID:9811605</ref> <ref>PMID:9734353</ref> <ref>PMID:9637688</ref> [[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> | + | [https://www.uniprot.org/uniprot/CDC20_HUMAN CDC20_HUMAN] Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation.<ref>PMID:9811605</ref> <ref>PMID:9734353</ref> <ref>PMID:9637688</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4ggd" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4ggd" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[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: Luo, X]] | + | [[Category: Luo X]] |
| - | [[Category: Tian, W]] | + | [[Category: Tian W]] |
| - | [[Category: Tomchick, D R]] | + | [[Category: Tomchick DR]] |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Mitosis]]
| + | |
| - | [[Category: Securin]]
| + | |
| - | [[Category: Ubiquitination]]
| + | |
| - | [[Category: Wd40]]
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| Structural highlights
Function
CDC20_HUMAN Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation.[1] [2] [3]
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kramer ER, Gieffers C, Holzl G, Hengstschlager M, Peters JM. Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family. Curr Biol. 1998 Nov 5;8(22):1207-10. PMID:9811605
- ↑ Fang G, Yu H, Kirschner MW. Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. Mol Cell. 1998 Aug;2(2):163-71. PMID:9734353
- ↑ Fang G, Yu H, Kirschner MW. The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes Dev. 1998 Jun 15;12(12):1871-83. PMID:9637688
- ↑ Tian W, Li B, Warrington R, Tomchick DR, Yu H, Luo X. Structural analysis of human Cdc20 supports multisite degron recognition by APC/C. 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 doi:http://dx.doi.org/10.1073/pnas.1213438109
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