6i41
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Co-crystal structure of human SPOP MATH domain (wild-type) and human BRD3 fragment== | |
| + | <StructureSection load='6i41' size='340' side='right'caption='[[6i41]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6i41]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I41 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I41 FirstGlance]. <br> | ||
| + | </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=6i41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i41 OCA], [http://pdbe.org/6i41 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i41 RCSB], [http://www.ebi.ac.uk/pdbsum/6i41 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i41 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/BRD3_HUMAN BRD3_HUMAN]] Note=A chromosomal aberration involving BRD3 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;9)(q14;q34) with NUT which produces a BRD3-NUT fusion protein. | ||
| + | == 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> [[http://www.uniprot.org/uniprot/BRD3_HUMAN BRD3_HUMAN]] Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling and interaction with transcription factors. Regulates transcription by promoting the binding of the transcription factor GATA1 to its targets (By similarity). Regulates transcription of the CCND1 gene.<ref>PMID:18406326</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | BET proteins such as BRD3 are oncogenic transcriptional coactivators. SPOP binding triggers their proteasomal degradation. In both endometrial and prostate cancers, SPOP mutations occur in the MATH domain, but with opposed influence on drug susceptibility. In prostate cancer, SPOP mutations presumably cause increased BET levels, decreasing BET inhibitor drug susceptibility. As opposed, in endometrial cancer, decreased BET levels concomitant with higher BET inhibitor drug susceptibility were observed. Here, we present the to our knowledge first co-crystal structure of SPOP and a bromodomain containing protein (BRD3). Our structural and biophysical data confirm the suggested loss-of-function in prostate cancer-associated SPOP mutants and provide mechanistic explanation. As opposed to previous literature, our data on endometrial cancer-associated SPOP mutants do not show altered binding behavior compared to wild-type SPOP, indicating a more complex regulatory mechanism. SPOP mutation screening may thus be considered a valuable personalized medicine tool for effective antitumor therapy. | ||
| - | + | Structural Insights into BET Client Recognition of Endometrial and Prostate Cancer-Associated SPOP Mutants.,Ostertag MS, Hutwelker W, Plettenburg O, Sattler M, Popowicz GM J Mol Biol. 2019 Apr 23. pii: S0022-2836(19)30213-X. doi:, 10.1016/j.jmb.2019.04.017. PMID:31026449<ref>PMID:31026449</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6i41" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ostertag, M S]] | ||
| + | [[Category: Popowicz, G M]] | ||
| + | [[Category: Sattler, M]] | ||
| + | [[Category: Ligase]] | ||
| + | [[Category: Ligase nuclear cancer ubiquitination]] | ||
Revision as of 11:19, 10 May 2019
Co-crystal structure of human SPOP MATH domain (wild-type) and human BRD3 fragment
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