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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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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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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...
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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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GTPases and their Regulation02:14

GTPases and their Regulation

8.7K
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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Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
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Related Experiment Video

Updated: Sep 18, 2025

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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Computational model predicts function of Rho-GTPase binding for plexin receptor GAP activity on Rap1b via dynamic

Nisha Bhattarai1, Lindsay Morrison2, Alexandre F Gomes2

  • 1Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, USA.

Protein Science : a Publication of the Protein Society
|June 23, 2025
PubMed
Summary

Plexin-GTPase interactions were simulated, revealing distinct dynamics and network changes when bound to single versus multiple GTPases. These findings clarify plexin signaling mechanisms.

Keywords:
GTPasesdynamic allosteryhydrogen‐deuterium exchangemolecular dynamics simulationsplexin transmembrane receptorprotein‐protein interactions

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Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein GST-RhoAG17A from Epithelial Cell Lysates
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Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein GST-RhoAG17A from Epithelial Cell Lysates

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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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Related Experiment Videos

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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-RhoAG17A from Epithelial Cell Lysates
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Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein GST-RhoAG17A from Epithelial Cell Lysates

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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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Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Structural Biology

Background:

  • Plexin-semaphorin signaling is crucial for cell migration, neuronal development, angiogenesis, and immune responses.
  • Plexins directly bind active Rho- and Ras-family GTPases via intracellular domains, including Rho-GTPase binding and GTPase-activating protein (GAP) segments.
  • The structural dynamics of plexin-GTPase interactions, especially with multiple GTPases, remain incompletely understood.

Purpose of the Study:

  • To investigate the conformational dynamics and network alterations in plexin-B1 when bound to single versus multiple GTPases.
  • To compare the binding stability and interaction networks of plexin-B1 with Rap1b (Ras), Rnd1 (Rho), and Rac1 (Rho) under different binding conditions.

Main Methods:

  • Molecular dynamics simulations were performed on six distinct plexin-B1-GTPase bound systems.
  • Analysis included conformational changes, network centralities, and interaction stability.
  • Computational models were validated against experimental hydrogen-deuterium exchange mass spectrometry data.

Main Results:

  • Plexin-B1 dynamics were more altered with Rac1 compared to Rnd1, depending on Rap1b binding to the GAP domain.
  • Rnd1 showed stronger, more stable interactions with plexin-B1 without Rap1b, whereas Rac1 exhibited fewer, less stable connections.
  • Network dynamics differed significantly when plexin-B1 was bound to both Ras and Rho-GTPases versus a single GTPase.

Conclusions:

  • Computational models provide insights into the molecular mechanisms of plexin-GTPase interactions.
  • Understanding these dynamics is key to deciphering complex GTPase signaling pathways.
  • The findings align with experimental data, enhancing our comprehension of plexin-mediated cellular processes.