View source for 4zlr


==Structure of the Brat-NHL domain bound to consensus RNA motif==
<StructureSection load='4zlr' size='340' side='right'caption='[[4zlr]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zlr]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZLR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4zlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zlr OCA], [https://pdbe.org/4zlr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zlr RCSB], [https://www.ebi.ac.uk/pdbsum/4zlr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zlr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BRAT_DROME BRAT_DROME] Plays a central role in translation repression of hb mRNA by being recruited by nos and pum to the Nanos Response Element (NRE), a 16 bp sequence in the hb mRNA 3'-UTR. Probably recruited by other proteins to repress translation of other mRNAs in other tissues. Involved in the regulation of ribosomal RNA synthesis and cell growth. Participates in abdominal segmentation and imaginal disk development. Involved in brain tumor suppression, by acting as a growth suppressor in the larval brain.<ref>PMID:11274060</ref> <ref>PMID:11807032</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
TRIM-NHL proteins are conserved among metazoans and control cell fate decisions in various stem cell linages. The Drosophila TRIM-NHL protein Brain tumor (Brat) directs differentiation of neuronal stem cells by suppressing self-renewal factors. Brat is an RNA-binding protein and functions as a translational repressor. However, it is unknown which RNAs Brat regulates and how RNA-binding specificity is achieved. Using RNA immunoprecipitation and RNAcompete, we identify Brat-bound mRNAs in Drosophila embryos and define consensus binding motifs for Brat as well as a number of additional TRIM-NHL proteins, indicating that TRIM-NHL proteins are conserved, sequence-specific RNA-binding proteins. We demonstrate that Brat-mediated repression and direct RNA-binding depend on the identified motif and show that binding of the localization factor Miranda to the Brat-NHL domain inhibits Brat activity. Finally, to unravel the sequence specificity of the NHL domain, we crystallize the Brat-NHL domain in complex with RNA and present a high-resolution protein-RNA structure of this fold.

The Crystal Structure of the NHL Domain in Complex with RNA Reveals the Molecular Basis of Drosophila Brain-Tumor-Mediated Gene Regulation.,Loedige I, Jakob L, Treiber T, Ray D, Stotz M, Treiber N, Hennig J, Cook KB, Morris Q, Hughes TR, Engelmann JC, Krahn MP, Meister G Cell Rep. 2015 Nov 10;13(6):1206-20. doi: 10.1016/j.celrep.2015.09.068. Epub 2015, Oct 29. PMID:26527002<ref>PMID:26527002</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zlr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Jakob L]]
[[Category: Loedige I]]
[[Category: Meister G]]
[[Category: Stotz M]]
[[Category: Treiber N]]
[[Category: Treiber T]]