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2ovr

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2ovr, resolution 2.50Å ()
Sites: , , , , , , , , , , and
Ligands:
Non-Standard Residues:
Gene: SKP1A, EMC19, OCP2, SKP1, TCEB1L (Homo sapiens), FBXW7, FBW7, FBX30, SEL10 (Homo sapiens)
Related: 2ovp, 2ovq
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Structure of the Skp1-Fbw7-CyclinEdegN complex

Publication Abstract from PubMed

The ubiquitin-mediated proteolysis of cyclin E plays a central role in cell-cycle progression, and cyclin E accumulation is a common event in cancer. Cyclin E degradation is triggered by multisite phosphorylation, which induces binding to the SCF(Fbw7) ubiquitin ligase complex. Structures of the Skp1-Fbw7 complex bound to cyclin E peptides identify a doubly phosphorylated pThr380/pSer384 cyclin E motif as an optimal, high-affinity degron and a singly phosphorylated pThr62 motif as a low-affinity one. Biochemical data indicate that the closely related yeast SCF(Cdc4) complex recognizes the multisite phosphorylated Sic1 substrate similarly and identify three doubly phosphorylated Sic1 degrons, each capable of high-affinity interactions with two Cdc4 phosphate binding sites. A model that explains the role of multiple cyclin E/Sic1 degrons is provided by the findings that Fbw7 and Cdc4 dimerize, that Fbw7 dimerization enhances the turnover of a weakly associated cyclin E in vivo, and that Cdc4 dimerization increases the rate and processivity of Sic1 ubiquitination in vitro.

Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases., Hao B, Oehlmann S, Sowa ME, Harper JW, Pavletich NP, Mol Cell. 2007 Apr 13;26(1):131-43. PMID:17434132

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2ovr is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Hao B, Oehlmann S, Sowa ME, Harper JW, Pavletich NP. Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol Cell. 2007 Apr 13;26(1):131-43. PMID:17434132 doi:http://dx.doi.org/10.1016/j.molcel.2007.02.022
  • Orlicky S, Tang X, Neduva V, Elowe N, Brown ED, Sicheri F, Tyers M. An allosteric inhibitor of substrate recognition by the SCF(Cdc4) ubiquitin ligase. Nat Biotechnol. 2010 Jul;28(7):733-7. Epub 2010 Jun 27. PMID:20581844 doi:10.1038/nbt.1646

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