アロステリーの起源とタンパク質の進化性:事例研究
Arjun S Raman1, K Ian White1, Rama Ranganathan2
1Green Center for Systems Biology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
Cell
|June 21, 2016
まとめ
新しい機能へのタンパク質の適応は,活性部位から遠く離れた突然変異に依存しています. これらのクラスブリッジング変異は,アロステリーがどのようにタンパク質から生じるかを明らかにします.
科学分野:
- タンパク質工学と構造生物学
- 進化生物学と分子進化について
背景:
- タンパク質は新しい機能の進化に 欠かせない適応力を備えています
- タンパク質の適応の構造的な基礎を理解することは 進化の鍵です
研究 の 目的:
- 新しいリガンド特異性へのタンパク質適応の基礎となる構造的原理を調査する.
- PDZ領域における進化的適応を媒介する突然変異の役割を調査する.
主な方法:
- 新しいリガンドクラスへの適応時にPDZ領域の構造変化の分析.
- リガンド結合部位から遠く離れたクラスブリッジング中間変異の特定.
- 進化的に保存された共進化アミノ酸ネットワーク (セクター) の特徴.
主要な成果:
- 適応は,好ましくは,活性部位から遠くにあるクラスブリッジング変異によって起こります.
- これらの変異は,異なるリガンドのクラスを機能的に結びつけ,条件付きの中立性を示します.
- クラス・ブリッジング変異はアロステリック変化を誘発し,形状の可塑性を高め,既存の機能を保存しながら新しい機能を可能にします.
- クラスを橋渡しするフェノタイプは,活性部位と離れた表面領域を結ぶ保存された共進化セクター内の変異と関連しています.
結論:
- タンパク質のアロステリックメカニズムは,機能的な要求からではなく,適応能力から生じます.
- この研究は,タンパク質の進化と機能的多様化における遠隔アロステリック変異の重要性を強調しています.
- 保存された共進化ネットワーク (セクター) は,タンパク質の適応と進化性を媒介する上で重要な役割を果たします.
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