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相关概念视频

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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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:
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The Ras Gene02:38

The Ras Gene

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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...
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GTPases and their Regulation02:14

GTPases and their Regulation

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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,...
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Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

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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...
6.7K
Rab Cascades01:25

Rab Cascades

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Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
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Rab Proteins01:14

Rab Proteins

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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...
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相关实验视频

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

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小型GTPase MRAS是一个破碎的开关.

Gabriela Bernal Astrain1,2, Regina Strakhova1,2, Chang Hwa Jo1

  • 1Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, QC, H3T 1J4, Canada.

Nature communications
|January 14, 2025
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概括

MRAS GTPase 不能作为一个分子开关,即使在激活突变的情况下也保持GDP负载. 这挑战了RAS GTPases的传统模型,并建议重新解释之前的MRAS研究.

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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

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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
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相关实验视频

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

  • 分子生物学分子生物学
  • 细胞信号传输 细胞信号传输
  • 生物化学 生物化学

背景情况:

  • RAS超级家族蛋白质是关键的信号分子.
  • 小GTPases通常被理解为分子开关的功能.
  • MRAS GTPase是NRAS和KRAS的密切同类物,调节MAPK活动.

研究的目的:

  • 为了研究MRAS GTPase的核酸结合和切换机制.
  • 为了确定MRAS是否作为经典的GDP/GTP分子开关而起作用.
  • 重新评估MRAS在细胞信号通路中的功能.

主要方法:

  • 在溶液和脂质双层上进行了体外核酸交换试验.
  • 对MRAS与GEF SOS1.1.的相互作用进行分析.
  • 在活细胞中以同位素标记的MRAS的NMR光谱.
  • 合成激活突变的表征.

主要成果:

  • 在溶液中或脂质双层上,MRAS无法将GDP与GTP进行交换.
  • 关氨酸核酸交换因子SOS1不能挽救这个缺陷.
  • 据认为激活MRAS的合成突变不会增加核酸交换,而是从GDP负载状态促进效应因子结合.
  • 活细胞NMR证实MRAS仍然是GDP负载的,即使在所谓的激活突变中也是如此.

结论:

  • MRAS 不像传统的 GDP/GTP 分子开关一样工作.
  • 观察到的MRAS功能可能独立于GTP负载.
  • 目前对MRAS的理解和实验方法可能需要重新解释.