核孔を通過するタンパク質の通過率を決定する表面特性
Steffen Frey1, Renate Rees1, Jürgen Schünemann1
1Department of Cellular Logistics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Cell
|June 30, 2018
まとめ
分子の表面特性は,核孔複合体 (NPC) 経由での輸送速度に決定的な影響を及ぼします. 再設計されたタンパク質は 劇的に変化した経路速度を示し 受容器媒介の核輸送にも 影響を及ぼします
科学分野:
- 分子生物学
- 細胞生物学
- バイオ物理学
背景:
- 核孔複合体 (NPC) は,選択的障壁を介して核と細胞質の間の輸送を調節する.
- NPC内のFGドメインバリアは分子を通過を制御します.
研究 の 目的:
- 移動性種の表面特性がNPCを通じた転移率にどのように影響するかを調査する.
- 分子通過の原理を理解し,それを輸送率の設計に適用する.
主な方法:
- NPC経路への充電,極性,水害性残留物の影響の分析.
- カチオン-π相互作用などの潜在的な相互作用を探求するための計算モデリング.
- 表面特性を改変した緑色光タンパク質 (GFP) の変種を設計する.
- 変化した輸送特性を持つエンジニアリングされたGFP変数の構造分析.
主要な成果:
- 負の電荷とライジンはNPCの通過を阻害し,水害性残留物,特定の極性残留物 (Cys,His) とアルギニンはそれを促進する.
- 設計されたGFPの変種は,野生型よりも35倍遅いから約500倍速く,広範囲のトランジット速度を示しました.
- 最速のGFPは自然核伝送受容体 (NTR) の輸送速度を上回った.
- 構造的な洞察は,エンジニアリングされた受容体がFGモチーフを効果的に結合することを明らかにしました.
- 貨物表面の性質は,NTRによる輸送でも,転移率に大きな影響を及ぼします.
結論:
- 分子表面の性質は,NPC通過率の重要な決定因子です.
- 合理的な設計は タンパク質の輸送運動を劇的に変化させ 自然な輸送効率を上回ります
- 核輸送の効率には,受容器媒介経路を含む貨物の特性が重要な役割を果たします.
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