5n10
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Cucurbit[8]uril and 14-3-3 based binary bivalent supramolecular-protein assembly platform== | |
| + | <StructureSection load='5n10' size='340' side='right' caption='[[5n10]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5n10]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N10 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N10 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C8L:CUCURBIT[8]URIL'>C8L</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5n10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n10 OCA], [http://pdbe.org/5n10 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n10 RCSB], [http://www.ebi.ac.uk/pdbsum/5n10 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n10 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN]] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref> [[http://www.uniprot.org/uniprot/1433B_HUMAN 1433B_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2.<ref>PMID:17717073</ref> <ref>PMID:19592491</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Interactions between proteins frequently employ recognition sequences that engage in multivalent binding events. Dimeric 14-3-3 adapter proteins represent a prominent example, typically binding partner proteins in a phosphorylation-dependent mono- or bivalent manner. Here we describe the development of a cucurbit[8]uril (Q8)-based supramolecular system, which in conjunction with the 14-3-3 protein dimer acts as a binary and bivalent protein assembly platform. We fused the phenylalanine-glycine-glycine (FGG) tripeptide motif to the N-terminus of the 14-3-3-binding epitope of the estrogen receptor alpha (ERalpha), for selective binding to Q8. Q8-induced dimerization of the ERalpha epitope augmented its affinity towards 14-3-3 via a binary bivalent binding mode. The crystal structure of the Q8-induced ternary complex, a first of its kind, reveals molecular insights into the multiple supramolecular interactions between the protein, peptide and Q8. | ||
| - | + | Cucurbit[8]uril and 14-3-3 based binary bivalent supramolecular-protein assembly platform and co-crystal structure.,de Vink P, Briels J, Schrader T, Milroy L, Brunsveld L, Ottmann C Angew Chem Int Ed Engl. 2017 May 16. doi: 10.1002/anie.201701807. PMID:28510303<ref>PMID:28510303</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5n10" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Ottmann, C]] | ||
| + | [[Category: Vink, P J.de]] | ||
| + | [[Category: Host-guest]] | ||
| + | [[Category: Scaffold protein]] | ||
| + | [[Category: Supramolecular complex]] | ||
| + | [[Category: Transcription]] | ||
Revision as of 13:38, 24 May 2017
Cucurbit[8]uril and 14-3-3 based binary bivalent supramolecular-protein assembly platform
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