View source for 7luo


==N-terminus of Skp2 bound to Cyclin A==
<StructureSection load='7luo' size='340' side='right'caption='[[7luo]], [[Resolution|resolution]] 3.17&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7luo]] 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=7LUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LUO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.17&#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=7luo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7luo OCA], [https://pdbe.org/7luo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7luo RCSB], [https://www.ebi.ac.uk/pdbsum/7luo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7luo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CCNA2_HUMAN CCNA2_HUMAN] Essential for the control of the cell cycle at the G1/S (start) and the G2/M (mitosis) transitions.[https://www.uniprot.org/uniprot/SKP2_HUMAN SKP2_HUMAN] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, MLL, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration.<ref>PMID:12435635</ref> <ref>PMID:11931757</ref> <ref>PMID:12840033</ref> <ref>PMID:12769844</ref> <ref>PMID:15342634</ref> <ref>PMID:16262255</ref> <ref>PMID:15949444</ref> <ref>PMID:16103164</ref> <ref>PMID:15668399</ref> <ref>PMID:16951159</ref> <ref>PMID:16581786</ref> <ref>PMID:17908926</ref> <ref>PMID:17962192</ref> <ref>PMID:22770219</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Skp2 and cyclin A are cell-cycle regulators that control the activity of CDK2. Cyclin A acts as an activator and substrate recruitment factor of CDK2, while Skp2 mediates the ubiquitination and subsequent destruction of the CDK inhibitor protein p27. The N terminus of Skp2 can interact directly with cyclin A but is not required for p27 ubiquitination. To gain insight into this poorly understood interaction, we have solved the 3.2 A X-ray crystal structure of the N terminus of Skp2 bound to cyclin A. The structure reveals a bipartite mode of interaction with two motifs in Skp2 recognizing two discrete surfaces on cyclin A. The uncovered binding mechanism allows for a rationalization of the inhibitory effect of Skp2 on CDK2-cyclin A kinase activity toward the RxL motif containing substrates and raises the possibility that other intermolecular regulators and substrates may use similar non-canonical modes of interaction for cyclin targeting.

Bipartite binding of the N terminus of Skp2 to cyclin A.,Kelso S, Orlicky S, Beenstock J, Ceccarelli DF, Kurinov I, Gish G, Sicheri F Structure. 2021 Sep 2;29(9):975-988.e5. doi: 10.1016/j.str.2021.04.011. Epub 2021 , May 13. PMID:33989513<ref>PMID:33989513</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7luo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ceccarelli DF]]
[[Category: Kelso S]]
[[Category: Sicheri F]]