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| | ==A ubiquitin ligase-substrate complex== | | ==A ubiquitin ligase-substrate complex== |
| - | <StructureSection load='4i6j' size='340' side='right' caption='[[4i6j]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4i6j' size='340' side='right'caption='[[4i6j]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4i6j]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I6J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I6J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4i6j]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I6J FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4i6e|4i6e]], [[4i6g|4i6g]]</td></tr> | + | </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=4i6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i6j OCA], [https://pdbe.org/4i6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i6j RCSB], [https://www.ebi.ac.uk/pdbsum/4i6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i6j ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cry2, Kiaa0658 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), FBXL3, FBL3A, FBXL3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SKP1, EMC19, OCP2, SKP1A, TCEB1L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4i6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i6j OCA], [http://pdbe.org/4i6j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i6j RCSB], [http://www.ebi.ac.uk/pdbsum/4i6j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i6j ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SKP1_HUMAN SKP1_HUMAN]] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. 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.<ref>PMID:16209941</ref> <ref>PMID:20181953</ref> [[http://www.uniprot.org/uniprot/FBXL3_HUMAN FBXL3_HUMAN]] Substrate-recognition component of the SCF(FBXL3) E3 ubiquitin ligase complex involved in circadian rhythm function. Plays a key role in the maintenance of both the speed and the robustness of the circadian clock oscillation. The SCF(FBXL3) complex mainly acts in the nucleus and mediates ubiquitination and subsequent degradation of CRY1 and CRY2. Activity of the SCF(FBXL3) complex is counteracted by the SCF(FBXL21) complex. FBXL3 probably recognizes and binds phosphorylated CRY1 and CRY2.<ref>PMID:17463251</ref> <ref>PMID:23452855</ref> | + | [https://www.uniprot.org/uniprot/CRY2_MOUSE CRY2_MOUSE] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4i6j" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4i6j" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cryptochrome 3D structures|Cryptochrome 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Bush, M F]] | + | [[Category: Mus musculus]] |
| - | [[Category: Busino, L]] | + | [[Category: Bush MF]] |
| - | [[Category: Hinds, T R]] | + | [[Category: Busino L]] |
| - | [[Category: Marionni, S T]] | + | [[Category: Hinds TR]] |
| - | [[Category: Pagano, M]] | + | [[Category: Marionni ST]] |
| - | [[Category: Saifee, N H]] | + | [[Category: Pagano M]] |
| - | [[Category: Xing, W]] | + | [[Category: Saifee NH]] |
| - | [[Category: Zheng, N]] | + | [[Category: Xing W]] |
| - | [[Category: Circadian clock]]
| + | [[Category: Zheng N]] |
| - | [[Category: F-box]]
| + | |
| - | [[Category: Lrr]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Period]]
| + | |
| - | [[Category: Photolyase fold]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Ubiquitination]]
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| Structural highlights
Function
CRY2_MOUSE
Publication Abstract from PubMed
The cryptochrome (CRY) flavoproteins act as blue-light receptors in plants and insects, but perform light-independent functions at the core of the mammalian circadian clock. To drive clock oscillations, mammalian CRYs associate with the Period proteins (PERs) and together inhibit the transcription of their own genes. The SCF(FBXL3) ubiquitin ligase complex controls this negative feedback loop by promoting CRY ubiquitination and degradation. However, the molecular mechanisms of their interactions and the functional role of flavin adenine dinucleotide (FAD) binding in CRYs remain poorly understood. Here we report crystal structures of mammalian CRY2 in its apo, FAD-bound and FBXL3-SKP1-complexed forms. Distinct from other cryptochromes of known structures, mammalian CRY2 binds FAD dynamically with an open cofactor pocket. Notably, the F-box protein FBXL3 captures CRY2 by simultaneously occupying its FAD-binding pocket with a conserved carboxy-terminal tail and burying its PER-binding interface. This novel F-box-protein-substrate bipartite interaction is susceptible to disruption by both FAD and PERs, suggesting a new avenue for pharmacological targeting of the complex and a multifaceted regulatory mechanism of CRY ubiquitination.
SCFFBXL3 ubiquitin ligase targets cryptochromes at their cofactor pocket.,Xing W, Busino L, Hinds TR, Marionni ST, Saifee NH, Bush MF, Pagano M, Zheng N Nature. 2013 Apr 4;496(7443):64-8. doi: 10.1038/nature11964. Epub 2013 Mar 17. PMID:23503662[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Xing W, Busino L, Hinds TR, Marionni ST, Saifee NH, Bush MF, Pagano M, Zheng N. SCFFBXL3 ubiquitin ligase targets cryptochromes at their cofactor pocket. Nature. 2013 Apr 4;496(7443):64-8. doi: 10.1038/nature11964. Epub 2013 Mar 17. PMID:23503662 doi:http://dx.doi.org/10.1038/nature11964
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