タンパク質の進化. タンパク質-タンパク質インターフェースにおける浸透性変性およびエピスタシス
Anna I Podgornaia1, Michael T Laub2
1Computational & Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science (New York, N.Y.)
|February 7, 2015
まとめ
研究者は,Escherichia coliのタンパク質キナーゼ PhoQの機能的配列空間をマッピングし,PhoQ-PhoPインターフェイスで広範な変性および文脈依存的効果 (epistasis) を明らかにしました. これはPhoQの進化を制約し,機能的変種よりも低いオートログの多様性をもたらします.
科学分野:
- 分子生物学は分子生物学である.
- プロテイン工学は,タンパク質の
- システム生物学 システム生物学
背景:
- タンパク質の配列空間をマッピングすることは,タンパク質の機能と進化を理解するために重要です.
- タンパク質キナーゼ PhoQ は,その基板 PhoP を認識し,細菌のシグナル伝達において重要な相互作用をします.
- PhoQの配列-機能関係を理解することは,その規制メカニズムを解読するために不可欠です.
研究 の 目的:
- Escherichia coli PhoQ.における主要な残留物の機能的配列空間を体系的にマッピングする.
- PhoQ-PhoPインターフェイスにおける変性およびエピスタシスの程度を調査する.
- 配列空間接続性がPhoQの進化をどのように制約するかを理解するために.
主な方法:
- 4つのキーポジションで16万種類のPhoQのバリエーションを備えた包括的なライブラリを作成.
- 次の世代のシーケンシングと組み合わせた2段階の選択プロセスを利用します.
- 配列関数関係の分析と機能変数の識別.
主要な成果:
- 生成されたライブラリから1659の機能的なPhoQ変種を特定しました.
- PhoQ-PhoPインターフェースの広範な退化が明らかにされ,複数の配列が機能性タンパク質を生成することを示しています.
- アミノ酸置換の効果は,その周囲の文脈に大きく依存する重要なエピスタシスを観察した.
結論:
- エピスタシスと遺伝子コードは,PhoQ配列空間における機能的変異の構造的な接続性を生み出します.
- この接続性は,PhoQ.の進化軌道を制約する可能性がある.
- 観察されたPhoQのオートログの多様性は,機能的なPhoQの多様性よりも著しく低い.
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