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4bh6

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Insights into degron recognition by APC coactivators from the structure of an Acm1-Cdh1 complex

Structural highlights

4bh6 is a 16 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4bh6"

@@ Line 3: / Line 3: @@
 <StructureSection load='4bh6' size='340' side='right'caption='[[4bh6]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4bh6]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. 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>
+<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]] 2.9&#8491;</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>
 == Function ==
-[[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>  [[https://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;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Atcc 18824]]
 [[Category: Large Structures]]
-[[Category: Barford, D]]
+[[Category: Saccharomyces cerevisiae]]
-[[Category: Chao, W C.H]]
+[[Category: Barford D]]
-[[Category: Cronin, N]]
+[[Category: Chao WCH]]
-[[Category: He, J]]
+[[Category: Cronin N]]
-[[Category: Yang, J]]
+[[Category: He J]]
-[[Category: Zhang, Z]]
+[[Category: Yang J]]
-[[Category: Acm1]]
+[[Category: Zhang Z]]
-[[Category: Anaphase promoting complex]]
-[[Category: Cell cycle]]
-[[Category: D box]]
-[[Category: Ubiquitination]]

4bh6

From Proteopedia

Current revision

Insights into degron recognition by APC coactivators from the structure of an Acm1-Cdh1 complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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