2LLQ

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

2LLQ の概要

• エントリーDOI: 10.2210/pdb2llq/pdb
• 関連するPDBエントリー: 2LLO
• NMR情報: BMRB: 18084
• 分子名称: Calmodulin, Estrogen receptor, CALCIUM ION (3 entities in total)
• 機能のキーワード: metal binding protein-hormone receptor complex, metal binding protein/hormone receptor
• 由来する生物種: Xenopus laevis (clawed frog,common platanna,platanna); 詳細
• 細胞内の位置: Isoform 1: Nucleus. Isoform 3: Nucleus. Nucleus: P03372
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 10020.27

構造登録者

Zhang, Y. (登録日: 2011-11-15, 公開日: 2012-02-01, 最終更新日: 2024-05-01)

主引用文献

Zhang, Y.,Li, Z.,Sacks, D.B.,Ames, J.B.
Structural basis for Ca2+-induced activation and dimerization of estrogen receptor alpha by calmodulin.
J.Biol.Chem., 287:9336-9344, 2012

PubMed 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.

PubMed: 22275375
DOI: 10.1074/jbc.M111.334797

実験手法

SOLUTION NMR