9be0: Difference between revisions
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The | ==GC-centric NF-kappaB RelA binding DNA== | ||
<StructureSection load='9be0' size='340' side='right'caption='[[9be0]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9be0]] is a 24 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=9BE0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BE0 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]] 2.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=9be0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9be0 OCA], [https://pdbe.org/9be0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9be0 RCSB], [https://www.ebi.ac.uk/pdbsum/9be0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9be0 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The dimeric nuclear factor kappa B (NF-kappaB) transcription factors (TFs) regulate gene expression by binding to a variety of kappaB DNA elements with conserved G:C-rich flanking sequences enclosing a degenerate central region. Toward defining mechanistic principles of affinity regulated by degeneracy, we observed an unusual dependence of the affinity of RelA on the identity of the central base pair, which appears to be noncontacted in the complex crystal structures. The affinity of kappaB sites with A or T at the central position is ~10-fold higher than with G or C. The crystal structures of neither the complexes nor the free kappaB DNAs could explain the differences in affinity. Interestingly, differential dynamics of several residues were revealed in molecular dynamics simulation studies, where simulation replicates totaling 148 mus were performed on NF-kappaB:DNA complexes and free kappaB DNAs. Notably, Arg187 and Arg124 exhibited selectivity in transient interactions that orchestrated a complex interplay among several DNA-interacting residues in the central region. Binding and simulation studies with mutants supported these observations of transient interactions dictating specificity. In combination with published reports, this work provides insights into the nuanced mechanisms governing the discriminatory binding of NF-kappaB family TFs to kappaB DNA elements and sheds light on cancer pathogenesis of cRel, a close homolog of RelA. | |||
Transient interactions modulate the affinity of NF-kappaB transcription factors for DNA.,Li T, Shahabi S, Biswas T, Tsodikov OV, Pan W, Huang DB, Wang VY, Wang Y, Ghosh G Proc Natl Acad Sci U S A. 2024 Jun 4;121(23):e2405555121. doi: , 10.1073/pnas.2405555121. Epub 2024 May 28. PMID:38805268<ref>PMID:38805268</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 9be0" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Ghosh | <references/> | ||
[[Category: Shahabi | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Biswas T]] | |||
[[Category: Ghosh G]] | |||
[[Category: Shahabi S]] | |||
[[Category: Tsodikov OV]] | |||
Latest revision as of 08:45, 7 August 2024
GC-centric NF-kappaB RelA binding DNAGC-centric NF-kappaB RelA binding DNA
Structural highlights
Publication Abstract from PubMedThe dimeric nuclear factor kappa B (NF-kappaB) transcription factors (TFs) regulate gene expression by binding to a variety of kappaB DNA elements with conserved G:C-rich flanking sequences enclosing a degenerate central region. Toward defining mechanistic principles of affinity regulated by degeneracy, we observed an unusual dependence of the affinity of RelA on the identity of the central base pair, which appears to be noncontacted in the complex crystal structures. The affinity of kappaB sites with A or T at the central position is ~10-fold higher than with G or C. The crystal structures of neither the complexes nor the free kappaB DNAs could explain the differences in affinity. Interestingly, differential dynamics of several residues were revealed in molecular dynamics simulation studies, where simulation replicates totaling 148 mus were performed on NF-kappaB:DNA complexes and free kappaB DNAs. Notably, Arg187 and Arg124 exhibited selectivity in transient interactions that orchestrated a complex interplay among several DNA-interacting residues in the central region. Binding and simulation studies with mutants supported these observations of transient interactions dictating specificity. In combination with published reports, this work provides insights into the nuanced mechanisms governing the discriminatory binding of NF-kappaB family TFs to kappaB DNA elements and sheds light on cancer pathogenesis of cRel, a close homolog of RelA. Transient interactions modulate the affinity of NF-kappaB transcription factors for DNA.,Li T, Shahabi S, Biswas T, Tsodikov OV, Pan W, Huang DB, Wang VY, Wang Y, Ghosh G Proc Natl Acad Sci U S A. 2024 Jun 4;121(23):e2405555121. doi: , 10.1073/pnas.2405555121. Epub 2024 May 28. PMID:38805268[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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