4J26

Estrogen Receptor in complex with proline-flanked LXXLL peptides

4J26 の概要

• エントリーDOI: 10.2210/pdb4j26/pdb
• 関連するPDBエントリー: 3OLL 4J24
• 分子名称: Estrogen receptor beta, 12-mer Peptide, ESTRADIOL, ... (4 entities in total)
• 機能のキーワード: estrogen receptor, proline, lxxll, alpha-helix, structure stabilization, hormone receptor-peptide complex, hormone receptor/peptide
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q92731
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 57672.62

構造登録者

Fuchs, S.,Nguyen, H.D.,Phan, T.,Burton, M.,Nieto, L.,de Vries-van Leeuwen, I.,Schmidt, A.,Goodarzifard, M.,Agten, S.,Rose, R.,Ottmann, C.,Milroy, L.G.,Brunsveld, L. (登録日: 2013-02-04, 公開日: 2013-03-13, 最終更新日: 2023-11-08)

主引用文献

Fuchs, S.,Nguyen, H.D.,Phan, T.T.,Burton, M.F.,Nieto, L.,de Vries-van Leeuwen, I.J.,Schmidt, A.,Goodarzifard, M.,Agten, S.M.,Rose, R.,Ottmann, C.,Milroy, L.G.,Brunsveld, L.
Proline primed helix length as a modulator of the nuclear receptor-coactivator interaction
J.Am.Chem.Soc., 135:4364-4371, 2013

PubMed Abstract: Nuclear receptor binding to coactivator proteins is an obligate first step in the regulation of gene transcription. Nuclear receptors preferentially bind to an LXXLL peptide motif which is highly conserved throughout the 300 or so natural coactivator proteins. This knowledge has shaped current understanding of this fundamental protein-protein interaction, and continues to inspire the search for new drug therapies. However, sequence specificity beyond the LXXLL motif and the molecular functioning of flanking residues still requires urgent addressing. Here, ribosome display has been used to reassess the estrogen receptor for new and enlarged peptide recognition motifs, leading to the discovery of a potent and highly evolved PXLXXLLXXP binding consensus. Molecular modeling and X-ray crystallography studies have provided the molecular insights on the role of the flanking prolines in priming the length of the α-helix and enabling optimal interactions of the α-helix dipole and its surrounding amino acids with the surface charge clamp and the receptor activation function 2. These findings represent new structural parameters for modulating the nuclear receptor-coactivator interaction based on linear sequences of proteinogenic amino acids and for the design of chemically modified inhibitors.

PubMed: 23437920
DOI: 10.1021/ja311748r

実験手法

X-RAY DIFFRACTION (2.3 Å)