関連する実験動画
Updated: May 11, 2026

10:37
Comparing the Affinity of GTPase-binding Proteins using Competition Assays
Published on: October 8, 2015
RanGAPは,アルギニン指なしでGTPの水解を媒介する
Michael J Seewald1, Carolin Körner, Alfred Wittinghofer
1Max-Planck-Institut für molekulare Physiologie, Abteilung Strukturelle Biologie, Dortmund, Germany.
Nature
|February 8, 2002
まとめ
グアニンヌクレオチド結合タンパク質活性化タンパク質 (GAPs) は通常,アルギニン指メカニズムを使用します. しかし,Ran GTPaseを活性化するRanGAPは,この戦略を採用していません.
科学分野:
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- 分子生物学は分子生物学である.
背景:
- グアニンヌクレオチド結合タンパク質活性化タンパク質 (GAPs) は,Gタンパク質のGTP水解を加速する.
- "アルギニン指"メカニズムは,RasとRhoに関する研究によって明らかにされた,GAP作用のための提案された普遍的なモデルです.
- 核のRasに関連するタンパク質であるRanは,核細胞プラズマ輸送とミトスのプロセスを調節し,そのGTP結合形態はRanGAPとRanBP1.1によって水解されます.
研究 の 目的:
- RanGAPによるGTP水解のメカニズムを解明する.
- RanGAP-RanBP1-Ran三元複合体の機能の構造的基礎を調査する.
- RanGAPが保存アルギニン指メカニズムを使用しているかどうかを判断する.
主な方法:
- Ran-RanBP1-RanGAP三元複合体の基礎状態と移行状態の3次元構造的決定.
- GTPの水解のメカニズムを評価するための生化学実験.
主要な成果:
- Ran-RanBP1-RanGAP複合体の構造は,RanGAPがアルギニン指を用いていないことを明らかにしています.
- 生物化学的データによると,Ran自体は,GTPの急速な水解のためのコアメカニズムを提供していることを示しています.
- Ran内の触媒性グルタミン残基は,触媒作用に不可欠であり,正しい位置づけが必要です.
結論:
- RanGAP媒介のGTP水解は,RasとRhoで見られる確立されたアルギニン指メカニズムから逸脱する.
- RanGAPとRanBP1によって促進されるRanの内在的なGTPase活動は,その機能にとって極めて重要です.
- 構造的および生化学的洞察は,GTPase 調節における精密な触媒残留物の位置づけの重要性を強調しています.
関連する概念動画
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
Directionality of Nuclear Transport
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
Rab Proteins
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...

