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| | ==Insights into degron recognition by APC coactivators from the structure of an Acm1-Cdh1 complex== | | ==Insights into degron recognition by APC coactivators from the structure of an Acm1-Cdh1 complex== |
| - | <StructureSection load='4bh6' size='340' side='right' caption='[[4bh6]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='4bh6' size='340' side='right'caption='[[4bh6]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4bh6]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BH6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BH6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4bh6]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BH6 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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]] 2.9Å</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=4bh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bh6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bh6 RCSB], [http://www.ebi.ac.uk/pdbsum/4bh6 PDBsum]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=4bh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bh6 OCA], [https://pdbe.org/4bh6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bh6 RCSB], [https://www.ebi.ac.uk/pdbsum/4bh6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bh6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CDH1_YEAST CDH1_YEAST]] Activator protein that regulates the ubiquitin ligase activity and substrate specificity of the anaphase promoting complex/cyclosome (APC/C). During telophase and in the subsequent G1 phase of the cell cycle, recognizes and binds proteins containing a destruction box (D-box) and an additional degradation signal termed the KEN box including ASE1, CDC20, the B-type cyclins CLB2 and CLB3, the polo-like kinase CDC5 and HSL1, and recruits them in a C-box-dependent manner to the APC/C for ubiquitination and subsequent proteolysis. Required for exit from mitosis, cytokinesis and formation of prereplicative complexes in G1. Probably is the target of a BUB2-dependent spindle checkpoint pathway.<ref>PMID:10329618</ref> <ref>PMID:11566880</ref> <ref>PMID:11448992</ref> [[http://www.uniprot.org/uniprot/ACM1_YEAST ACM1_YEAST]] Negative regulator of GDH1, the activator protein that regulates the ubiquitin ligase activity and substrate specificity of the anaphase promoting complex/cyclosome (APC/C), and which is required for exit from mitosis, cytokinesis and formation of prereplicative complexes in G1.<ref>PMID:17030612</ref> | + | [https://www.uniprot.org/uniprot/CDH1_YEAST CDH1_YEAST] Activator protein that regulates the ubiquitin ligase activity and substrate specificity of the anaphase promoting complex/cyclosome (APC/C). During telophase and in the subsequent G1 phase of the cell cycle, recognizes and binds proteins containing a destruction box (D-box) and an additional degradation signal termed the KEN box including ASE1, CDC20, the B-type cyclins CLB2 and CLB3, the polo-like kinase CDC5 and HSL1, and recruits them in a C-box-dependent manner to the APC/C for ubiquitination and subsequent proteolysis. Required for exit from mitosis, cytokinesis and formation of prereplicative complexes in G1. Probably is the target of a BUB2-dependent spindle checkpoint pathway.<ref>PMID:10329618</ref> <ref>PMID:11566880</ref> <ref>PMID:11448992</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4bh6" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Barford, D]] | + | [[Category: Barford D]] |
| - | [[Category: Chao, W C.H]] | + | [[Category: Chao WCH]] |
| - | [[Category: Cronin, N]] | + | [[Category: Cronin N]] |
| - | [[Category: He, J]] | + | [[Category: He J]] |
| - | [[Category: Yang, J]] | + | [[Category: Yang J]] |
| - | [[Category: Zhang, Z]] | + | [[Category: Zhang Z]] |
| - | [[Category: Acm1]]
| + | |
| - | [[Category: Anaphase promoting complex]]
| + | |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: D box]]
| + | |
| - | [[Category: Ubiquitination]]
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| Structural highlights
Function
CDH1_YEAST Activator protein that regulates the ubiquitin ligase activity and substrate specificity of the anaphase promoting complex/cyclosome (APC/C). During telophase and in the subsequent G1 phase of the cell cycle, recognizes and binds proteins containing a destruction box (D-box) and an additional degradation signal termed the KEN box including ASE1, CDC20, the B-type cyclins CLB2 and CLB3, the polo-like kinase CDC5 and HSL1, and recruits them in a C-box-dependent manner to the APC/C for ubiquitination and subsequent proteolysis. Required for exit from mitosis, cytokinesis and formation of prereplicative complexes in G1. Probably is the target of a BUB2-dependent spindle checkpoint pathway.[1] [2] [3]
Publication Abstract from PubMed
The anaphase-promoting complex/cyclosome (APC/C) regulates sister chromatid segregation and the exit from mitosis. Selection of most APC/C substrates is controlled by coactivator subunits (either Cdc20 or Cdh1) that interact with substrate destruction motifs-predominantly the destruction (D) box and KEN box degrons. How coactivators recognize D box degrons and how this is inhibited by APC/C regulatory proteins is not defined at the atomic level. Here, from the crystal structure of S. cerevisiae Cdh1 in complex with its specific inhibitor Acm1, which incorporates D and KEN box pseudosubstrate motifs, we describe the molecular basis for D box recognition. Additional interactions between Acm1 and Cdh1 identify a third protein-binding site on Cdh1 that is likely to confer coactivator-specific protein functions including substrate association. We provide a structural rationalization for D box and KEN box recognition by coactivators and demonstrate that many noncanonical APC/C degrons bind APC/C coactivators at the D box coreceptor.
Insights into Degron Recognition by APC/C Coactivators from the Structure of an Acm1-Cdh1 Complex.,He J, Chao WC, Zhang Z, Yang J, Cronin N, Barford D Mol Cell. 2013 May 22. pii: S1097-2765(13)00329-8. doi:, 10.1016/j.molcel.2013.04.024. PMID:23707760[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Alexandru G, Zachariae W, Schleiffer A, Nasmyth K. Sister chromatid separation and chromosome re-duplication are regulated by different mechanisms in response to spindle damage. EMBO J. 1999 May 17;18(10):2707-21. PMID:10329618 doi:10.1093/emboj/18.10.2707
- ↑ Schwab M, Neutzner M, Mocker D, Seufert W. Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the ubiquitin ligase APC. EMBO J. 2001 Sep 17;20(18):5165-75. PMID:11566880 doi:10.1093/emboj/20.18.5165
- ↑ Huang JN, Park I, Ellingson E, Littlepage LE, Pellman D. Activity of the APC(Cdh1) form of the anaphase-promoting complex persists until S phase and prevents the premature expression of Cdc20p. J Cell Biol. 2001 Jul 9;154(1):85-94. PMID:11448992
- ↑ He J, Chao WC, Zhang Z, Yang J, Cronin N, Barford D. Insights into Degron Recognition by APC/C Coactivators from the Structure of an Acm1-Cdh1 Complex. Mol Cell. 2013 May 22. pii: S1097-2765(13)00329-8. doi:, 10.1016/j.molcel.2013.04.024. PMID:23707760 doi:10.1016/j.molcel.2013.04.024
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