Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2012 Mar 16;28712:9336-44. doi: 10.1074/jbc.M111.334797.
Show Gene links
Show Anatomy links
Structural basis for Ca2+-induced activation and dimerization of estrogen receptor α by calmodulin.
Zhang Y
,
Li Z
,
Sacks DB
,
Ames JB
.
???displayArticle.abstract???
The estrogen receptor α (ER-α) regulates expression of target genes implicated in development, metabolism, and breast cancer. Calcium-dependent regulation of ER-α 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-α (residues 287-305). A model of the complete CaM·ER-α 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-α (residues 292, 296, 299, 302, and 303), which explains why full-length CaM binds two molecules of ER-α in a 1:2 complex and stabilizes ER-α dimerization. Exposed glutamate residues in CaM (Glu(11), Glu(14), Glu(84), and Glu(87)) form salt bridges with key lysine residues in ER-α (Lys(299), Lys(302), and Lys(303)), which are likely to prevent ubiquitination at these sites and inhibit degradation of ER-α. Mutants of ER-α at the CaM-binding site (W292A and K299A) weaken binding to CaM, and I298E/K299D disrupts estrogen-induced transcription. CaM facilitates dimerization of ER-α in the absence of estrogen, and stimulation of ER-α by either Ca(2+) and/or estrogen may serve to regulate transcription in a combinatorial fashion.
Babu,
Structure of calmodulin refined at 2.2 A resolution.
1988, Pubmed
Babu,
Structure of calmodulin refined at 2.2 A resolution.
1988,
Pubmed
Berridge,
The versatility and universality of calcium signalling.
2000,
Pubmed
Berridge,
Calcium signalling: dynamics, homeostasis and remodelling.
2003,
Pubmed
Biswas,
Calmodulin is essential for estrogen receptor interaction with its motif and activation of responsive promoter.
1998,
Pubmed
Bouhoute,
Modulation of estradiol and DNA binding to estrogen receptor upon association with calmodulin.
1995,
Pubmed
Brandt,
Cooperativity and dimerization of recombinant human estrogen receptor hormone-binding domain.
1997,
Pubmed
Conway,
The estrogen receptor-alpha A908G (K303R) mutation occurs at a low frequency in invasive breast tumors: results from a population-based study.
2005,
Pubmed
Coticchia,
Calmodulin modulates Akt activity in human breast cancer cell lines.
2009,
Pubmed
Delaglio,
NMRPipe: a multidimensional spectral processing system based on UNIX pipes.
1995,
Pubmed
Dickson,
Estrogen receptor-mediated processes in normal and cancer cells.
2000,
Pubmed
Dominguez,
HADDOCK: a protein-protein docking approach based on biochemical or biophysical information.
2003,
Pubmed
Elshorst,
NMR solution structure of a complex of calmodulin with a binding peptide of the Ca2+ pump.
1999,
Pubmed
,
Xenbase
Gallo,
Calmodulin, a regulatory partner of the estrogen receptor alpha in breast cancer cells.
2008,
Pubmed
García Pedrero,
Calmodulin is a selective modulator of estrogen receptors.
2002,
Pubmed
Gopalakrishna,
Ca2+-induced hydrophobic site on calmodulin: application for purification of calmodulin by phenyl-Sepharose affinity chromatography.
1982,
Pubmed
Hall,
The multifaceted mechanisms of estradiol and estrogen receptor signaling.
2001,
Pubmed
Herynk,
Association between the estrogen receptor alpha A908G mutation and outcomes in invasive breast cancer.
2007,
Pubmed
Hoeflich,
Calmodulin in action: diversity in target recognition and activation mechanisms.
2002,
Pubmed
Huang,
The solution structure of the Mg2+ form of soybean calmodulin isoform 4 reveals unique features of plant calmodulins in resting cells.
2010,
Pubmed
Hurth,
Ligand-induced changes in estrogen receptor conformation as measured by site-directed spin labeling.
2004,
Pubmed
Ikura,
Solution structure of a calmodulin-target peptide complex by multidimensional NMR.
1992,
Pubmed
Ikura,
Calcium binding and conformational response in EF-hand proteins.
1996,
Pubmed
Ikura,
Genetic polymorphism and protein conformational plasticity in the calmodulin superfamily: two ways to promote multifunctionality.
2006,
Pubmed
Le Romancer,
Cracking the estrogen receptor's posttranslational code in breast tumors.
2011,
Pubmed
Levin,
Membrane oestrogen receptor alpha signalling to cell functions.
2009,
Pubmed
Li,
Calmodulin enhances the stability of the estrogen receptor.
2001,
Pubmed
Li,
Calmodulin regulates the transcriptional activity of estrogen receptors. Selective inhibition of calmodulin function in subcellular compartments.
2003,
Pubmed
Li,
The transcriptional activity of estrogen receptor-alpha is dependent on Ca2+/calmodulin.
2005,
Pubmed
Li,
E6AP and calmodulin reciprocally regulate estrogen receptor stability.
2006,
Pubmed
Li,
Functional interactions between calmodulin and estrogen receptor-alpha.
2007,
Pubmed
Maaroufi,
Estrogen receptor of primary breast cancers: evidence for intracellular proteolysis.
2000,
Pubmed
McKenna,
Nuclear receptor coregulators: cellular and molecular biology.
1999,
Pubmed
Meador,
Modulation of calmodulin plasticity in molecular recognition on the basis of x-ray structures.
1993,
Pubmed
Meyer,
Characterization of gelatine and acid soluble collagen by size exclusion chromatography coupled with multi angle light scattering (SEC-MALS).
2003,
Pubmed
Nawaz,
Proteasome-dependent degradation of the human estrogen receptor.
1999,
Pubmed
Osawa,
A novel target recognition revealed by calmodulin in complex with Ca2+-calmodulin-dependent kinase kinase.
1999,
Pubmed
Park,
Nuclear magnetic resonance structure of calcium-binding protein 1 in a Ca(2+) -bound closed state: implications for target recognition.
2011,
Pubmed
Raz,
Rapid estrogen signaling in the brain.
2008,
Pubmed
Rhoads,
Sequence motifs for calmodulin recognition.
1997,
Pubmed
Schumacher,
Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin.
2001,
Pubmed
Schwabe,
DNA recognition by the oestrogen receptor: from solution to the crystal.
1993,
Pubmed
Schwieters,
The Xplor-NIH NMR molecular structure determination package.
2003,
Pubmed
Shiau,
The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen.
1998,
Pubmed
Singer,
Cyclic nucleotide phosphodiesterases in neoplastic and nonneoplastic human mammary tissues.
1976,
Pubmed
Strahl,
Structural insights into activation of phosphatidylinositol 4-kinase (Pik1) by yeast frequenin (Frq1).
2007,
Pubmed
Tamrazi,
Estrogen receptor dimerization: ligand binding regulates dimer affinity and dimer dissociation rate.
2002,
Pubmed
Tanenbaum,
Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains.
1998,
Pubmed
Vassylyev,
Crystal structure of troponin C in complex with troponin I fragment at 2.3-A resolution.
1998,
Pubmed
Wang,
Direct acetylation of the estrogen receptor alpha hinge region by p300 regulates transactivation and hormone sensitivity.
2001,
Pubmed
Wishart,
The chemical shift index: a fast and simple method for the assignment of protein secondary structure through NMR spectroscopy.
1992,
Pubmed
Wood,
Estrogen response elements function as allosteric modulators of estrogen receptor conformation.
1998,
Pubmed
,
Xenbase
Wu,
Structural basis for an unexpected mode of SERM-mediated ER antagonism.
2005,
Pubmed
Wyatt,
Combined differential light scattering with various liquid chromatography separation techniques.
1991,
Pubmed
Yap,
Structural basis for simultaneous binding of two carboxy-terminal peptides of plant glutamate decarboxylase to calmodulin.
2003,
Pubmed
Zhang,
Structural basis for sequence specific DNA binding and protein dimerization of HOXA13.
2011,
Pubmed
Zweckstetter,
NMR: prediction of molecular alignment from structure using the PALES software.
2008,
Pubmed
van Dijk,
Information-driven protein-DNA docking using HADDOCK: it is a matter of flexibility.
2006,
Pubmed
