2LLQ: Solution nmr-derived structure of calmodulin c-lobe bound with er alpha peptide

Citation:
Abstract
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.
PDB ID: 2LLQDownload
MMDB ID: 96862
PDB Deposition Date: 2011/11/15
Updated in MMDB: 2013/08
Experimental Method:
solution nmr
Source Organism:
Xenopus laevis
Similar Structures:
Biological Unit for 2LLQ: dimeric; determined by author
Molecular Components in 2LLQ
Label Count Molecule
Proteins (2 molecules)
1
Calmodulin
Molecule annotation
1
Estrogen Receptor(Gene symbol: ESR1)
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

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