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==T95R mutant IRF4 DNA-binding domain bound to an DNA containing GAAA motif==
<StructureSection load='8jkn' size='340' side='right'caption='[[8jkn]], [[Resolution|resolution]] 2.92&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8jkn]] is a 8 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=8JKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JKN 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]] 2.92&#8491;</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=8jkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jkn OCA], [https://pdbe.org/8jkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jkn RCSB], [https://www.ebi.ac.uk/pdbsum/8jkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jkn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/F2Z3D5_HUMAN F2Z3D5_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Interferon regulatory factor 4 (IRF4) is a transcription factor that regulates the development and function of immune cells. Recently, a new multimorphic mutation T95R was identified in the IRF4 DNA-binding domain (DBD) in patients with autosomal dominant combined immune deficiency. Here, we characterized the interactions of the wild-type IRF4-DBD (IRF4-DBD(WT)) and T95R mutant (IRF4-DBD(T95R)) with a canonical DNA sequence and several noncanonical DNA sequences. We found that compared to IRF4-DBD(WT), IRF4-DBD(T95R) exhibits higher binding affinities for both canonical and noncanonical DNAs, with the highest preference for the noncanonical GATA sequence. The crystal structures of IRF4-DBD(WT) in complex with the GATA sequence and IRF4-DBD(T95R) in complexes with both canonical and noncanonical DNAs were determined, showing that the T95R mutation enhances the interactions of IRF4-DBD(T95R) with the canonical and noncanonical DNAs to achieve higher affinity and specificity. Collectively, our data provide the molecular basis for the gain-of-function and new function of IRF4(T95R).

Molecular basis for the functional roles of the multimorphic T95R mutation of IRF4 causing human autosomal dominant combined immunodeficiency.,Wang G, Feng X, Ding J Structure. 2023 Aug 31:S0969-2126(23)00293-9. doi: 10.1016/j.str.2023.08.013. PMID:37683642<ref>PMID:37683642</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8jkn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ding J]]
[[Category: Feng X]]
[[Category: Wang G]]