8CEF

Asymmetric Dimerization in a Transcription Factor Superfamily is Promoted by Allosteric Interactions with DNA

8CEF の概要

• エントリーDOI: 10.2210/pdb8cef/pdb
• 分子名称: DNA (26-MER), Nuclear receptor DNA binding domain, ZINC ION, ... (5 entities in total)
• 機能のキーワード: nuclear receptor, dna, steroid hormone receptor, hormone
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 116929.56

構造登録者

Patel, A.K.M.,Shaik, T.B.,McEwen, A.G.,Moras, D.,Klaholz, B.P.,Billas, I.M.L. (登録日: 2023-02-01, 公開日: 2023-08-09, 最終更新日: 2023-09-20)

主引用文献

Patel, A.K.M.,Vilela, P.,Shaik, T.B.,McEwen, A.G.,Hazemann, I.,Brillet, K.,Ennifar, E.,Hamiche, A.,Markov, G.V.,Laudet, V.,Moras, D.,Klaholz, B.P.,Billas, I.M.L.
Asymmetric dimerization in a transcription factor superfamily is promoted by allosteric interactions with DNA.
Nucleic Acids Res., 51:8864-8879, 2023

PubMed Abstract: Transcription factors, such as nuclear receptors achieve precise transcriptional regulation by means of a tight and reciprocal communication with DNA, where cooperativity gained by receptor dimerization is added to binding site sequence specificity to expand the range of DNA target gene sequences. To unravel the evolutionary steps in the emergence of DNA selection by steroid receptors (SRs) from monomeric to dimeric palindromic binding sites, we carried out crystallographic, biophysical and phylogenetic studies, focusing on the estrogen-related receptors (ERRs, NR3B) that represent closest relatives of SRs. Our results, showing the structure of the ERR DNA-binding domain bound to a palindromic response element (RE), unveil the molecular mechanisms of ERR dimerization which are imprinted in the protein itself with DNA acting as an allosteric driver by allowing the formation of a novel extended asymmetric dimerization region (KR-box). Phylogenetic analyses suggest that this dimerization asymmetry is an ancestral feature necessary for establishing a strong overall dimerization interface, which was progressively modified in other SRs in the course of evolution.

PubMed: 37503845
DOI: 10.1093/nar/gkad632

実験手法

X-RAY DIFFRACTION (2.486 Å)