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| | ==Solution NMR-derived structure of calmodulin N-lobe bound with ER alpha peptide== | | ==Solution NMR-derived structure of calmodulin N-lobe bound with ER alpha peptide== |
| - | <StructureSection load='2llo' size='340' side='right'caption='[[2llo]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2llo' size='340' side='right'caption='[[2llo]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2llo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/African_clawed_frog African clawed frog]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LLO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LLO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2llo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LLO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LLO FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2llq|2llq]]</div></td></tr> | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">calm1, calm2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog])</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=2llo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2llo OCA], [https://pdbe.org/2llo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2llo RCSB], [https://www.ebi.ac.uk/pdbsum/2llo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2llo ProSAT]</span></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=2llo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2llo OCA], [https://pdbe.org/2llo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2llo RCSB], [https://www.ebi.ac.uk/pdbsum/2llo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2llo ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CALM_XENLA CALM_XENLA]] Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. [[https://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>
| + | [https://www.uniprot.org/uniprot/CALM1_XENLA CALM1_XENLA] Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: African clawed frog]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Xenopus laevis]] |
| - | [[Category: Metal binding protein-hormone receptor complex]] | + | [[Category: Zhang Y]] |
| Structural highlights
Function
CALM1_XENLA Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases.
Publication Abstract from PubMed
The estrogen receptor alpha (ER-alpha) regulates expression of target genes implicated in development, metabolism, and breast cancer. Calcium-dependent regulation of ER-alpha is critical for activating gene expression and is controlled by calmodulin (CaM). Here, we present the NMR structures for the two lobes of CaM each bound to a localized region of ER-alpha (residues 287-305). A model of the complete CaM.ER-alpha complex was constructed by combining these two structures with additional data. The two lobes of CaM both compete for binding at the same site on ER-alpha (residues 292, 296, 299, 302, and 303), which explains why full-length CaM binds two molecules of ER-alpha in a 1:2 complex and stabilizes ER-alpha dimerization. Exposed glutamate residues in CaM (Glu(11), Glu(14), Glu(84), and Glu(87)) form salt bridges with key lysine residues in ER-alpha (Lys(299), Lys(302), and Lys(303)), which are likely to prevent ubiquitination at these sites and inhibit degradation of ER-alpha. Mutants of ER-alpha at the CaM-binding site (W292A and K299A) weaken binding to CaM, and I298E/K299D disrupts estrogen-induced transcription. CaM facilitates dimerization of ER-alpha in the absence of estrogen, and stimulation of ER-alpha by either Ca(2+) and/or estrogen may serve to regulate transcription in a combinatorial fashion.
Structural basis for Ca2+-induced activation and dimerization of estrogen receptor alpha by calmodulin.,Zhang Y, Li Z, Sacks DB, Ames JB J Biol Chem. 2012 Mar 16;287(12):9336-44. Epub 2012 Jan 23. PMID:22275375[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang Y, Li Z, Sacks DB, Ames JB. Structural basis for Ca2+-induced activation and dimerization of estrogen receptor alpha by calmodulin. J Biol Chem. 2012 Mar 16;287(12):9336-44. Epub 2012 Jan 23. PMID:22275375 doi:10.1074/jbc.M111.334797
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