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Related Concept Videos

Small GTPases - Ras and Rho01:24

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:
Directionality of Nuclear Transport01:42

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 Proteins01:14

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...
Coat Assembly and GTPases01:33

Coat Assembly and GTPases

Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Rab Cascades01:25

Rab Cascades

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.
GTPases and their Regulation02:14

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...

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Related Experiment Video

Updated: Jun 26, 2026

Comparing the Affinity of GTPase-binding Proteins using Competition Assays
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Published on: October 8, 2015

Guanine Exchange Factors Show Existence of Transient Pockets on Rac1 Surface.

Elvis A F Martis1, Morgane Rousselle2, Vincent Sauzeau2

  • 1US2B, Nantes Université, CNRS, UMR 6286, F-44000 Nantes, France.

Journal of Chemical Information and Modeling
|June 24, 2026
PubMed
Summary

Researchers identified transient binding pockets on Rac1, a key molecular switch, using advanced simulations. This discovery opens new possibilities for designing drugs targeting Rac1 regulation by guanine exchange factors (GEFs).

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Last Updated: Jun 26, 2026

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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Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein (GST-RhoA(G17A)) from Epithelial Cell Lysates
11:28

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein (GST-RhoA(G17A)) from Epithelial Cell Lysates

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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

Area of Science:

  • Molecular biology
  • Computational biophysics

Background:

  • Rac1 (Ras-related C3 botulinum toxin substrate 1) functions as a molecular switch.
  • Regulation of Rac1 involves guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs) due to slow GTP hydrolysis.
  • Rac1's small size and shallow surface were thought to make it undruggable.

Purpose of the Study:

  • To identify and characterize transient binding pockets on Rac1.
  • To explore potential druggable sites on Rac1 for GEF and GAP interactions.
  • To understand the dynamics of Rac1 pocket opening and closing.

Main Methods:

  • Molecular dynamics (MD) simulations.
  • Cosolvent molecular probes to sample open states of binding pockets.
  • Principal component analysis (PCA) of MD simulations to analyze domain movements.

Main Results:

  • Identified four transient binding pockets on Rac1.
  • Two pockets serve as general GEF binding sites.
  • A third pocket interacts with DOCK family GEFs, and the fourth binds ELMO1 protein.

Conclusions:

  • Transient pockets on Rac1 are accessible to GEF proteins.
  • These findings offer new strategies for Rac1-targeted drug design.
  • The study provides insights into the dynamic nature of Rac1 regulation.