4OND

Ancestral Steroid Receptor 2 DBD helix mutant - ERE DNA complex

4OND の概要

• エントリーDOI: 10.2210/pdb4ond/pdb
• 関連するPDBエントリー: 4OLN 4OOR
• 分子名称: Ancestral SR2 Helix Mutant, 5'-D(*CP*CP*AP*GP*GP*TP*CP*AP*GP*AP*GP*TP*GP*AP*CP*CP*TP*G)-3', 5'-D(*TP*CP*AP*GP*GP*TP*CP*AP*CP*TP*CP*TP*GP*AP*CP*CP*TP*G)-3', ... (5 entities in total)
• 機能のキーワード: nuclear receptor dna binding domain, zinc finger, transcription factor, coregulators, transcription-dna complex, transcription/dna
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 58744.63

構造登録者

Ortlund, E.O.,Murphy, M.N. (登録日: 2014-01-28, 公開日: 2014-10-29, 最終更新日: 2024-02-28)

主引用文献

McKeown, A.N.,Bridgham, J.T.,Anderson, D.W.,Murphy, M.N.,Ortlund, E.A.,Thornton, J.W.
Evolution of DNA specificity in a transcription factor family produced a new gene regulatory module.
Cell(Cambridge,Mass.), 159:58-68, 2014

PubMed Abstract: Complex gene regulatory networks require transcription factors (TFs) to bind distinct DNA sequences. To understand how novel TF specificity evolves, we combined phylogenetic, biochemical, and biophysical approaches to interrogate how DNA recognition diversified in the steroid hormone receptor (SR) family. After duplication of the ancestral SR, three mutations in one copy radically weakened binding to the ancestral estrogen response element (ERE) and improved binding to a new set of DNA sequences (steroid response elements, SREs). They did so by establishing unfavorable interactions with ERE and abolishing unfavorable interactions with SRE; also required were numerous permissive substitutions, which nonspecifically improved cooperativity and affinity of DNA binding. Our findings indicate that negative determinants of binding play key roles in TFs' DNA selectivity and-with our prior work on the evolution of SR ligand specificity during the same interval-show how a specific new gene regulatory module evolved without interfering with the integrity of the ancestral module.

PubMed: 25259920
DOI: 10.1016/j.cell.2014.09.003

実験手法

X-RAY DIFFRACTION (2.253 Å)