|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal Structure of the Human SPOP C-terminal Domain== | | ==Crystal Structure of the Human SPOP C-terminal Domain== |
| - | <StructureSection load='4hs2' size='340' side='right' caption='[[4hs2]], [[Resolution|resolution]] 1.53Å' scene=''> | + | <StructureSection load='4hs2' size='340' side='right'caption='[[4hs2]], [[Resolution|resolution]] 1.53Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hs2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HS2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hs2]] is a 1 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=4HS2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HS2 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPOP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4hs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hs2 OCA], [https://pdbe.org/4hs2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hs2 RCSB], [https://www.ebi.ac.uk/pdbsum/4hs2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hs2 ProSAT]</span></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=4hs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hs2 OCA], [http://pdbe.org/4hs2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hs2 RCSB], [http://www.ebi.ac.uk/pdbsum/4hs2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hs2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SPOP_HUMAN SPOP_HUMAN]] Inhibits IPF1/PDX1 transactivation of established target promoters, such as insulin, may be by recruiting a repressor complex (By similarity). In complex with CUL3, involved in ubiquitination of BMI1, H2AFY and DAXX, and probably also in ubiquitination and proteasomal degradation of Gli2 or Gli3.<ref>PMID:14528312</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref> | + | [https://www.uniprot.org/uniprot/SPOP_HUMAN SPOP_HUMAN] Inhibits IPF1/PDX1 transactivation of established target promoters, such as insulin, may be by recruiting a repressor complex (By similarity). In complex with CUL3, involved in ubiquitination of BMI1, H2AFY and DAXX, and probably also in ubiquitination and proteasomal degradation of Gli2 or Gli3.<ref>PMID:14528312</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 18: |
Line 17: |
| | </div> | | </div> |
| | <div class="pdbe-citations 4hs2" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4hs2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Speckle-type POZ protein 3D structures|Speckle-type POZ protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Carr, S B]] | + | [[Category: Large Structures]] |
| - | [[Category: Geersdaele, L K.Van]] | + | [[Category: Carr SB]] |
| - | [[Category: Stead, M A]] | + | [[Category: Stead MA]] |
| - | [[Category: Wright, S C]] | + | [[Category: Van Geersdaele LK]] |
| - | [[Category: Oligomerisation]] | + | [[Category: Wright SC]] |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Protein interaction domain]]
| + | |
| Structural highlights
Function
SPOP_HUMAN Inhibits IPF1/PDX1 transactivation of established target promoters, such as insulin, may be by recruiting a repressor complex (By similarity). In complex with CUL3, involved in ubiquitination of BMI1, H2AFY and DAXX, and probably also in ubiquitination and proteasomal degradation of Gli2 or Gli3.[1] [2] [3]
Publication Abstract from PubMed
Protein ubiquitination in eukaryotic cells is mediated by diverse E3 ligase enzymes that each target specific substrates. The cullin E3 ligase complexes are the most abundant class of E3 ligases; they contain various cullin components that serve as scaffolds for interaction with substrate-recruiting adaptor proteins. SPOP is a BTB-domain adaptor of the cullin-3 E3 ligase complexes; it selectively recruits substrates via its N-terminal MATH domain, whereas its BTB domain mediates dimerization and interactions with cullin-3. It has recently been recognized that the high-order oligomerization of SPOP enhances the ubiquitination of substrates. Here, a dimerization interface in the SPOP C-terminus is identified and it is shown that the dimerization interfaces of the BTB domain and of the C-terminus act independently and in tandem to generate high-order SPOP oligomers. The crystal structure of the dimeric SPOP C-terminal domain is reported at 1.5 A resolution and it is shown that Tyr353 plays a critical role in high-order oligomerization. A model of the high-order SPOP oligomer is presented that depicts a helical organization that could enhance the efficiency of substrate ubiquitination.
Structural basis of high-order oligomerization of the cullin-3 adaptor SPOP.,van Geersdaele LK, Stead MA, Harrison CM, Carr SB, Close HJ, Rosbrook GO, Connell SD, Wright SC Acta Crystallogr D Biol Crystallogr. 2013 Sep;69(Pt 9):1677-84. doi:, 10.1107/S0907444913012687. Epub 2013 Aug 15. PMID:23999291[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Furukawa M, He YJ, Borchers C, Xiong Y. Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases. Nat Cell Biol. 2003 Nov;5(11):1001-7. Epub 2003 Oct 5. PMID:14528312 doi:10.1038/ncb1056
- ↑ Hernandez-Munoz I, Lund AH, van der Stoop P, Boutsma E, Muijrers I, Verhoeven E, Nusinow DA, Panning B, Marahrens Y, van Lohuizen M. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7635-40. Epub 2005 May 16. PMID:15897469 doi:0408918102
- ↑ Kwon JE, La M, Oh KH, Oh YM, Kim GR, Seol JH, Baek SH, Chiba T, Tanaka K, Bang OS, Joe CO, Chung CH. BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase. J Biol Chem. 2006 May 5;281(18):12664-72. Epub 2006 Mar 8. PMID:16524876 doi:10.1074/jbc.M600204200
- ↑ van Geersdaele LK, Stead MA, Harrison CM, Carr SB, Close HJ, Rosbrook GO, Connell SD, Wright SC. Structural basis of high-order oligomerization of the cullin-3 adaptor SPOP. Acta Crystallogr D Biol Crystallogr. 2013 Sep;69(Pt 9):1677-84. doi:, 10.1107/S0907444913012687. Epub 2013 Aug 15. PMID:23999291 doi:http://dx.doi.org/10.1107/S0907444913012687
|
