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Related Concept Videos

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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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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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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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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Negative Regulator Molecules01:23

Negative Regulator Molecules

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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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Related Experiment Video

Updated: Sep 13, 2025

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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Structure and mechanism of the RalGAP tumor suppressor complex.

René Rasche1, Björn Udo Klink2,3, Lisa Helene Apken4

  • 1Institute of Biochemistry, University of Münster, Münster, Germany.

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Ral GTPase activating protein (RalGAP) complexes suppress cancer-driving Ras signals. We determined the RalGAP structure, revealing its tetrameric architecture and how subunits stabilize each other for in vivo function.

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Area of Science:

  • Structural biology
  • Molecular mechanisms
  • Cancer research

Background:

  • Ral GTPase activating protein (RalGAP) complexes are critical negative regulators of Ral GTPases.
  • They counteract oncogenic Ras signaling, acting as tumor suppressors.
  • Lack of structural data hindered understanding of RalGAP complex functionality.

Purpose of the Study:

  • To elucidate the structural architecture of RalGAP complexes.
  • To understand the molecular basis of RalGAP complex assembly and function.
  • To investigate the relevance of structural findings for cancer-associated mutations.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine the structure of RalGAP.
  • Biochemical assays to assess in vitro and in vivo activity.
  • Analysis of cancer patient-reported RalGAP subunit variants.

Main Results:

  • A cryo-EM structure revealed an extended 58 nm tetrameric architecture of RalGAP, composed of two heterodimers of RalGAPα and RalGAPβ subunits.
  • A unique domain of RalGAPβ stabilizes the catalytic domain of RalGAPα, explaining the necessity for heterodimer formation.
  • While tetramer formation is not essential for in vitro activity, it is crucial for in vivo function.
  • Analysis of cancer variants suggests impaired complex formation, impacting function.

Conclusions:

  • The determined RalGAP structure provides molecular insights into its tumor suppressor function.
  • Structural findings highlight the importance of RalGAP complex assembly for in vivo activity.
  • The study emphasizes the clinical relevance of RalGAP structural biology in understanding cancer.