4ggc
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ggc]] is a 1 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=4GGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GGC FirstGlance]. <br> | <table><tr><td colspan='2'>[[4ggc]] is a 1 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=4GGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GGC FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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]] 1.35Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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=4ggc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggc OCA], [https://pdbe.org/4ggc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ggc RCSB], [https://www.ebi.ac.uk/pdbsum/4ggc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ggc 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=4ggc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggc OCA], [https://pdbe.org/4ggc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ggc RCSB], [https://www.ebi.ac.uk/pdbsum/4ggc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ggc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[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> | [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;"> | ||
| - | == 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. | ||
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| - | 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> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4ggc" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Structural Analysis of Human Cdc20 Supports Multi-site Degron Recognition by APC/C
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