Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

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

3.3K
3.3K
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
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

12.4K
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...
12.4K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

19.2K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
19.2K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

8.3K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
8.3K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Degradation of G-quadruplex-binding proteins in chromatin using G4-ligand-based proteolysis-targeting chimeras.

Nature chemistry·2026
Same author

Design, Synthesis, and Biological Evaluation of Pseudo-Natural Products Inspired by Aryloctahydroindole Alkaloids.

ChemMedChem·2026
Same author

Covalent modification of a glutamic acid inspired by HaloTag technology.

Nature communications·2026
Same author

Targeting a Glutamic Acid in PDEδ with Fluoromethyl-Aryl Electrophiles Impairs K-Ras Signaling.

Journal of medicinal chemistry·2026
Same author

Monovalent pseudo-natural products supercharge degradation of IDO1 by its native E3 KLHDC3.

Nature chemistry·2026
Same author

Overcoming Ligand Discovery Challenges: Developing Peptide-Based Tracers for SPSB2.

ACS chemical biology·2025
Same journal

Proton Transfer Shuttle Mediated Dormant-Active Balance for Accelerated and Controlled Polymerization of N-Carboxyanhydrides.

Angewandte Chemie (International ed. in English)·2026
Same journal

Chloride-Regulated Depolymerization of Aluminosilicate Networks for Fast Ion Transport Compliant Interfaces in Sustainable All-Solid-State Sodium Batteries.

Angewandte Chemie (International ed. in English)·2026
Same journal

Asymmetric Zn─N<sub>2</sub>O-Coordinated Hydrogen-Bonded Organic Frameworks for Electrochemical Hydrogen Peroxide Production and Wastewater Purification.

Angewandte Chemie (International ed. in English)·2026
Same journal

Photocatalytic Cascade Nitrogen Fixation for Selective Purification of Methane-Rich Coal-Bed Gas Over a Bimetallic MOF.

Angewandte Chemie (International ed. in English)·2026
Same journal

Scalable Art-Inspired Tessellated Covalent Organic Framework Membranes Enable Highly Selective Ion Separation.

Angewandte Chemie (International ed. in English)·2026
Same journal

Layered Copper-Anthraquinone Coordination Polymer Cathode Leveraging Dual-Redox Sites and Facilitated Ion Diffusion for High-Performance Lithium-Ion Batteries.

Angewandte Chemie (International ed. in English)·2026
See all related articles

Related Experiment Video

Updated: Mar 31, 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

10.4K

Direct Modulation of Small GTPase Activity and Function.

Philipp M Cromm1,2, Jochen Spiegel1,2, Tom N Grossmann3,4,5

  • 1Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund (Germany).

Angewandte Chemie (International Ed. in English)
|October 17, 2015
PubMed
Summary
This summary is machine-generated.

Small GTPases, crucial cellular switches, are implicated in diseases. Recent strategies, including novel cavity targeting, are making these previously "undruggable" proteins promising for drug discovery.

Keywords:
cancerdrug designinhibitorsproteinssmall GTPases

More Related Videos

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

9.7K
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

11.3K

Related Experiment Videos

Last Updated: Mar 31, 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

10.4K
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

9.7K
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

11.3K

Area of Science:

  • Biochemistry and Molecular Biology
  • Cellular Signaling
  • Drug Discovery

Background:

  • Small GTPases function as molecular switches regulating vital cellular processes.
  • Dysregulation of small GTPases is linked to various human diseases, making them attractive drug targets.
  • Historically, small GTPases have been considered 'undruggable' due to challenges in direct modulation.

Purpose of the Study:

  • To provide an overview of the small GTPase superfamily.
  • To summarize recent advancements in targeting small GTPases.
  • To discuss future perspectives for modulating these proteins in drug discovery.

Main Methods:

  • Review of existing literature on small GTPases.
  • Analysis of novel targeting strategies, including transient cavity identification.
  • Synthesis of biological insights and drug development approaches.

Main Results:

  • Identification of novel transient cavities on small GTPase surfaces.
  • Development of new strategies for targeting small GTPases beyond Ras.
  • Increased attention on various small GTPases as viable drug targets.

Conclusions:

  • Recent progress offers new hope for developing direct modulators of small GTPases.
  • Small GTPases represent promising targets for therapeutic intervention in various diseases.
  • Continued research into novel targeting strategies is essential for clinical success.