6qmq

NF-YB/C Heterodimer in Complex with NF-YA-derived Peptide Stabilized with C8-Hydrocarbon LinkerNF-YB/C Heterodimer in Complex with NF-YA-derived Peptide Stabilized with C8-Hydrocarbon Linker

Structural highlights 6qmq is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: , , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nuclear transcription factor Y

spinqualitylabelsall models 6qmq, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image