View source for 6qmp


==NF-YB/C Heterodimer in Complex with NF-YA Peptide==
<StructureSection load='6qmp' size='340' side='right'caption='[[6qmp]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qmp]] is a 3 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=6QMP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QMP 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=6qmp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qmp OCA], [https://pdbe.org/6qmp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qmp RCSB], [https://www.ebi.ac.uk/pdbsum/6qmp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qmp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NFYA_HUMAN NFYA_HUMAN] Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors. NF-YA positively regulates the transcription of the core clock component ARNTL/BMAL1.<ref>PMID:12741956</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein complex formation highly depends on the interplay between preorganization and flexibility of involved binding epitopes. The design of epitope mimetics mainly focuses on the stabilization of a particular bioactive conformation often not considering the conformational dynamics. This limits the potential of peptidomimetics in particular when aiming for challenging targets such as transcription factors. Here, we report the first peptide-derived inhibitor of the NF-Y transcription factor by first constraining the conformation of an epitope using the hydrocarbon stapling approach and then fine-tuning its flexibility. In the initial set of constrained peptides, we observed a severe effect of a single non-interacting alpha-methyl group on complex stability. The combination of X-ray and NMR structures as well as isothermal titration calorimetry and CD spectroscopy reveal how this methyl group affects the conformation of the peptide in its bound state. Adaption of the methylation pattern results in a peptide which inhibits transcription factor assembly and its subsequent recruitment to the target DNA. These results highlight the importance of residual conformational freedom when constraining protein fragments in their bioactive conformation.

A peptide with fine-tuned flexibility inhibits NF-Y transcription factor assembly.,Jeganathan S, Wendt M, Kiehstaller S, Brancaccio D, Kuepper A, Pospiech N, Carotenuto A, Novellino E, Hennig S, Grossmann TN Angew Chem Int Ed Engl. 2019 Sep 20. doi: 10.1002/anie.201907901. PMID:31539186<ref>PMID:31539186</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qmp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Nuclear transcription factor Y|Nuclear transcription factor Y]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Grossmann TN]]
[[Category: Hennig S]]
[[Category: Jeganathan S]]
[[Category: Kiehstaller S]]
[[Category: Pearce NM]]
[[Category: Wendt M]]