View source for 6tlj


==Cryo-EM structure of the Anaphase-promoting complex/Cyclosome, in complex with the Mitotic checkpoint complex (APC/C-MCC) at 3.8 angstrom resolution==
<SX load='6tlj' size='340' side='right' viewer='molstar' caption='[[6tlj]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6tlj]] is a 12 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=6TLJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TLJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.8&#8491;</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=6tlj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tlj OCA], [https://pdbe.org/6tlj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tlj RCSB], [https://www.ebi.ac.uk/pdbsum/6tlj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tlj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CDC23_HUMAN CDC23_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.<ref>PMID:18485873</ref> 
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== Publication Abstract from PubMed ==
The anaphase-promoting complex (APC/C) is the key E3 ubiquitin ligase which directs mitotic progression and exit by catalysing the sequential ubiquitination of specific substrates. The activity of the APC/C in mitosis is restrained by the spindle assembly checkpoint (SAC), which coordinates chromosome segregation with the assembly of the mitotic spindle. The SAC effector is the mitotic checkpoint complex (MCC), which binds and inhibits the APC/C. It is incompletely understood how the APC/C switches substrate specificity in a cell cycle-specific manner. For instance, it is unclear how in prometaphase, when APC/C activity towards cyclin B and securin is repressed by the MCC, the kinase Nek2A is ubiquitinated. Here, we combine biochemical and structural analysis with functional studies in cells to show that Nek2A is a conformational-specific binder of the APC/C-MCC complex (APC/C(MCC) ) and that, in contrast to cyclin A, Nek2A can be ubiquitinated efficiently by the APC/C in conjunction with both the E2 enzymes UbcH10 and UbcH5. We propose that these special features of Nek2A allow its prometaphase-specific ubiquitination.

A unique binding mode of Nek2A to the APC/C allows its ubiquitination during prometaphase.,Alfieri C, Tischer T, Barford D EMBO Rep. 2020 Apr 19:e49831. doi: 10.15252/embr.201949831. PMID:32307883<ref>PMID:32307883</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6tlj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Alfieri C]]
[[Category: Barford D]]