2Q1V

Ancestral corticoid receptor in complex with cortisol

2Q1V の概要

• エントリーDOI: 10.2210/pdb2q1v/pdb
• 関連するPDBエントリー: 2Q1H
• 分子名称: AncCR, 17,21-DIHYDROXYPREGNA-1,4-DIENE-3,11,20-TRIONE, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: nuclear receptor, cortisol, corticoid, evolution, common ancestor, mineralocorticoid, transcription
• 由来する生物種: unidentified
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29503.23

構造登録者

Ortlund, E.A.,Redinbo, M.R. (登録日: 2007-05-25, 公開日: 2007-09-04, 最終更新日: 2024-04-03)

主引用文献

Ortlund, E.A.,Bridgham, J.T.,Redinbo, M.R.,Thornton, J.W.
Crystal structure of an ancient protein: evolution by conformational epistasis.
Science, 317:1544-1548, 2007

PubMed Abstract: The structural mechanisms by which proteins have evolved new functions are known only indirectly. We report x-ray crystal structures of a resurrected ancestral protein-the approximately 450 million-year-old precursor of vertebrate glucocorticoid (GR) and mineralocorticoid (MR) receptors. Using structural, phylogenetic, and functional analysis, we identify the specific set of historical mutations that recapitulate the evolution of GR's hormone specificity from an MR-like ancestor. These substitutions repositioned crucial residues to create new receptor-ligand and intraprotein contacts. Strong epistatic interactions occur because one substitution changes the conformational position of another site. "Permissive" mutations-substitutions of no immediate consequence, which stabilize specific elements of the protein and allow it to tolerate subsequent function-switching changes-played a major role in determining GR's evolutionary trajectory.

PubMed: 17702911
DOI: 10.1126/science.1142819

実験手法

X-RAY DIFFRACTION (1.95 Å)