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Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

5.7K
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:
5.7K
GTPases and their Regulation02:14

GTPases and their Regulation

10.3K
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,...
10.3K
GTPases and their Regulation02:14

GTPases and their Regulation

3.2K
No description available
3.2K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

12.3K
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...
12.3K
The Ras Gene02:38

The Ras Gene

7.5K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
7.5K
Rab Proteins01:14

Rab Proteins

5.4K
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...
5.4K

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関連する実験動画

Updated: Mar 23, 2026

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
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Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

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K-Ras (G12C) 阻害剤は,GTPの親和性と効果因子の相互作用をアロステリックに制御する.

Jonathan M Ostrem1, Ulf Peters, Martin L Sos

  • 11] Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, California 94158, USA [2].

Nature
|November 22, 2013
PubMed
まとめ

研究者らは,K-Ras (G12C) がん変異を標的とした新しい小分子を開発した. これらの阻害剤は不可逆的に結合し,新しい標的となる部位を作り,変異体特有の治療戦略を提供します.

さらに関連する動画

Comparing the Affinity of GTPase-binding Proteins using Competition Assays
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Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Published on: October 8, 2015

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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

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関連する実験動画

Last Updated: Mar 23, 2026

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
13:51

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

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Comparing the Affinity of GTPase-binding Proteins using Competition Assays
10:37

Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Published on: October 8, 2015

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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

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科学分野:

  • 腫瘍学 腫瘍学
  • 分子生物学は分子生物学である.
  • ドラッグ・ディスカバリー・ドリッグ・ディスカバリー・ドリッグ・ディスカバリー・ドリッグ・ディスカバリー

背景:

  • K-Rasの体内の変異は,がんではよく見られ,治療の結果が悪いことに関連しています.
  • K-Rasを直接標的にすることは,GTP/GDPに対する高い親和性と,既知のアロステリック部位の欠如のために困難です.
  • 腫瘍性K-Ras変異はGTPの水解を阻害し,活性GTP結合Ras.の割合を増加させます.

研究 の 目的:

  • 腫瘍性K-Ras (G12C) 変異体を選択的に標的にする小分子を開発する.
  • K-Ras (((G12C)) の新しいアロステル結合部位を特定し,検証する.

主な方法:

  • K-Ras (((G12C) に特異的な不可逆的な小分子阻害剤の開発.
  • 結晶学的研究により,結合メカニズムを明らかにし,新しいポケットを特定します.
  • ヌクレオチド結合とエフェクタ相互作用を評価するための生化学分析.

主要な成果:

  • 変異したシステイン経由でK-Ras (G12C) に特異的に結合する不可逆的阻害剤が開発されました.
  • 結晶学では,スイッチII領域の下にある新しい結合ポケットが明らかになった.
  • 阻害剤の結合はスイッチIとスイッチIIを妨害し,ニュクレオチド偏好をGTPからGDPにシフトさせ,Raf結合を損なう.

結論:

  • K-Ras (((G12C) の新しい,突然変異特有のアロステリックサイトが特定され,検証されました.
  • これらの発見は,K-Ras (G12C) 変異がんに対する標的治療の開発のための構造ベースの戦略を提供します.