View source for 8dtu


==The complex of nanobody 5344N74D with BCL11A ZF6.==
<StructureSection load='8dtu' size='340' side='right'caption='[[8dtu]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dtu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DTU 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]] 2.447&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8dtu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dtu OCA], [https://pdbe.org/8dtu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dtu RCSB], [https://www.ebi.ac.uk/pdbsum/8dtu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dtu ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/BC11A_HUMAN BC11A_HUMAN] Hereditary persistence of fetal hemoglobin - beta-thalassemia. Chromosomal aberrations involving BCL11A may be a cause of lymphoid malignancies. Translocation t(2;14)(p13;q32.3) causes BCL11A deregulation and amplification.<ref>PMID:11719382</ref>   The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:27453576</ref> 
== Function ==
[https://www.uniprot.org/uniprot/BC11A_HUMAN BC11A_HUMAN] Transcription factor associated with the BAF SWI/SNF chromatin remodeling complex (By similarity). Repressor of fetal hemoglobin (HbF) level (PubMed:26375765). Involved in brain development (PubMed:27453576). Functions as a myeloid and B-cell proto-oncogene. May play important roles in leukemogenesis and hematopoiesis. Essential factor in lymphopoiesis required for B-cell formation in fetal liver. May function as a modulator of the transcriptional repression activity of ARP1 (By similarity).[UniProtKB:Q9QYE3]<ref>PMID:26375765</ref> <ref>PMID:27453576</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Transcription factors (TFs) control numerous genes that are directly relevant to many human disorders. However, developing specific reagents targeting TFs within intact cells is challenging due to the presence of highly disordered regions within these proteins. Intracellular antibodies offer opportunities to probe protein function and validate therapeutic targets. Here, we describe the optimization of nanobodies specific for BCL11A, a validated target for the treatment of hemoglobin disorders. We obtained first-generation nanobodies directed to a region of BCL11A comprising zinc fingers 4 to 6 (ZF456) from a synthetic yeast surface display library, and employed error-prone mutagenesis, structural determination, and molecular modeling to enhance binding affinity. Engineered nanobodies recognized ZF6 and mediated targeted protein degradation (TPD) of BCL11A protein in erythroid cells, leading to the anticipated reactivation of fetal hemoglobin (HbF) expression. Evolved nanobodies distinguished BCL11A from its close paralog BCL11B, which shares an identical DNA-binding specificity. Given the ease of manipulation of nanobodies and their exquisite specificity, nanobody-mediated TPD of TFs should be suitable for dissecting regulatory relationships of TFs and gene targets and validating therapeutic potential of proteins of interest.

Evolution of nanobodies specific for BCL11A.,Yin M, Izadi M, Tenglin K, Viennet T, Zhai L, Zheng G, Arthanari H, Dassama LMK, Orkin SH Proc Natl Acad Sci U S A. 2023 Jan 17;120(3):e2218959120. doi: , 10.1073/pnas.2218959120. Epub 2023 Jan 10. PMID:36626555<ref>PMID:36626555</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8dtu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Dassama LM]]
[[Category: Orkin SH]]
[[Category: Tenglin K]]
[[Category: Yin M]]
[[Category: Zhai L]]