8jko: Difference between revisions
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==T95R mutant IRF4 DNA-binding domain bound to an DNA containing GATA motif== | |||
<StructureSection load='8jko' size='340' side='right'caption='[[8jko]], [[Resolution|resolution]] 2.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8jko]] 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=8JKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JKO 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]] 2.95Å</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=8jko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jko OCA], [https://pdbe.org/8jko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jko RCSB], [https://www.ebi.ac.uk/pdbsum/8jko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jko 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Ding | <div class="pdbe-citations 8jko" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Ding J]] | |||
[[Category: Feng X]] | |||
[[Category: Wang G]] | |||
Latest revision as of 14:46, 20 September 2023
T95R mutant IRF4 DNA-binding domain bound to an DNA containing GATA motif
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