3rtr

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==A RING E3-substrate complex poised for ubiquitin-like protein transfer: structural insights into cullin-RING ligases==
==A RING E3-substrate complex poised for ubiquitin-like protein transfer: structural insights into cullin-RING ligases==
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<StructureSection load='3rtr' size='340' side='right' caption='[[3rtr]], [[Resolution|resolution]] 3.21&Aring;' scene=''>
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<StructureSection load='3rtr' size='340' side='right'caption='[[3rtr]], [[Resolution|resolution]] 3.21&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3rtr]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RTR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RTR FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3rtr]] is a 8 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=3RTR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RTR FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.21&#8491;</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CUL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), RBX1, RNF75, ROC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rtr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rtr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rtr RCSB], [http://www.ebi.ac.uk/pdbsum/3rtr PDBsum]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3rtr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rtr OCA], [https://pdbe.org/3rtr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rtr RCSB], [https://www.ebi.ac.uk/pdbsum/3rtr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rtr ProSAT]</span></td></tr>
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<table>
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</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/CUL1_HUMAN CUL1_HUMAN] Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO11) does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110 (By similarity).<ref>PMID:9663463</ref> <ref>PMID:15531760</ref> <ref>PMID:15640526</ref> <ref>PMID:18644861</ref> <ref>PMID:19679664</ref>
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How RING E3 ligases mediate E2-to-substrate ubiquitin-like protein (UBL) transfer remains unknown. Here we address how the RING E3 RBX1 positions NEDD8's E2 (UBC12) and substrate (CUL1). We find that existing structures are incompatible with CUL1 NEDD8ylation and report a new conformation of RBX1 that places UBC12 adjacent to CUL1. We propose RING domain rotation as a general mechanism for UBL transfer for the largest family of E3s.
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A RING E3-substrate complex poised for ubiquitin-like protein transfer: structural insights into cullin-RING ligases.,Calabrese MF, Scott DC, Duda DM, Grace CR, Kurinov I, Kriwacki RW, Schulman BA Nat Struct Mol Biol. 2011 Jul 17;18(8):947-9. doi: 10.1038/nsmb.2086. PMID:21765416<ref>PMID:21765416</ref>
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
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*[[Cullin 3D structures|Cullin 3D structures]]
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*[[Ring box protein 3D structures|Ring box protein 3D structures]]
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*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Calabrese, M F.]]
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[[Category: Large Structures]]
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[[Category: Duda, D M.]]
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[[Category: Calabrese MF]]
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[[Category: Grace, C R.]]
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[[Category: Duda DM]]
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[[Category: Kriwacki, R W.]]
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[[Category: Grace CR]]
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[[Category: Kurinov, I.]]
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[[Category: Kriwacki RW]]
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[[Category: Schulman, B A.]]
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[[Category: Kurinov I]]
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[[Category: Scott, D C.]]
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[[Category: Schulman BA]]
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[[Category: Cullin]]
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[[Category: Scott DC]]
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[[Category: E3 ligase]]
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[[Category: Ligase]]
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[[Category: Nedd8]]
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[[Category: Ubiquitin]]
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[[Category: Ubl conjugation pathway]]
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Current revision

A RING E3-substrate complex poised for ubiquitin-like protein transfer: structural insights into cullin-RING ligases

PDB ID 3rtr

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