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6qms

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Revision as of 05:20, 8 September 2022

NF-YB/C Heterodimer in Complex with NF-YA-derived Peptide Stabilized with C11-Hydrocarbon Linker

Structural highlights

6qms 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.
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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kawata H, Yamada K, Shou Z, Mizutani T, Yazawa T, Yoshino M, Sekiguchi T, Kajitani T, Miyamoto K. Zinc-fingers and homeoboxes (ZHX) 2, a novel member of the ZHX family, functions as a transcriptional repressor. Biochem J. 2003 Aug 1;373(Pt 3):747-57. PMID:12741956 doi:10.1042/BJ20030171
↑ Jeganathan S, Wendt M, Kiehstaller S, Brancaccio D, Kuepper A, Pospiech N, Carotenuto A, Novellino E, Hennig S, Grossmann TN. A peptide with fine-tuned flexibility inhibits NF-Y transcription factor assembly. Angew Chem Int Ed Engl. 2019 Sep 20. doi: 10.1002/anie.201907901. PMID:31539186 doi:http://dx.doi.org/10.1002/anie.201907901

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6qms"

@@ Line 3: / Line 3: @@
 <StructureSection load='6qms' size='340' side='right'caption='[[6qms]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6qms]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QMS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6qms]] 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=6QMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QMS FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=L4R:'>L4R</scene>, <scene name='pdbligand=MH8:(2S)-2-AMINO-2-METHYLHEPT-6-ENOIC+ACID'>MH8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
+</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=L4R:Fmoc-(R)-2-(7-octenyl)alanine'>L4R</scene>, <scene name='pdbligand=MH8:(2S)-2-AMINO-2-METHYLHEPT-6-ENOIC+ACID'>MH8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NFYB, HAP3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NFYC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6qms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qms OCA], [https://pdbe.org/6qms PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qms RCSB], [https://www.ebi.ac.uk/pdbsum/6qms PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qms 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>  [[https://www.uniprot.org/uniprot/NFYC_HUMAN NFYC_HUMAN]] Stimulates the transcription of various genes by recognizing and binding to a CCAAT motif in promoters, for example in type 1 collagen, albumin and beta-actin genes. [[https://www.uniprot.org/uniprot/NFYB_HUMAN NFYB_HUMAN]] Stimulates the transcription of various genes by recognizing and binding to a CCAAT motif in promoters, for example in type 1 collagen, albumin and beta-actin genes.
+[[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 ==
@@ Line 26: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Grossmann, T N]]
+[[Category: Grossmann TN]]
-[[Category: Hennig, S]]
+[[Category: Hennig S]]
-[[Category: Jeganathan, S]]
+[[Category: Jeganathan S]]
-[[Category: Kiehstaller, S]]
+[[Category: Kiehstaller S]]
-[[Category: Pearce, N M]]
+[[Category: Pearce NM]]
-[[Category: Wendt, M]]
+[[Category: Wendt M]]
-[[Category: Stapled peptide histone fold transcription factor]]
-[[Category: Transcription]]

6qms

From Proteopedia

Revision as of 05:20, 8 September 2022

NF-YB/C Heterodimer in Complex with NF-YA-derived Peptide Stabilized with C11-Hydrocarbon Linker

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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