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Related Concept Videos

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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GTPases and their Regulation02:14

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Protein-protein Interfaces02:04

Protein-protein Interfaces

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Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
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Coat Assembly and GTPases01:33

Coat Assembly and GTPases

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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.
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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.
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The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

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The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
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Related Experiment Video

Updated: Feb 16, 2026

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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CDC42 binds PAK4 via an extended GTPase-effector interface.

Byung Hak Ha1, Titus J Boggon2,3

  • 1Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520.

Proceedings of the National Academy of Sciences of the United States of America
|January 4, 2018
PubMed
Summary
This summary is machine-generated.

The p21-activated kinase 4 (PAK4) interacts with CDC42 through its CRIB domain and other regions. These interactions uniquely regulate PAK4 kinase activity and binding affinity.

Keywords:
crystal structureprotein kinaseprotein–protein interactionsignal transductionsmall GTPase

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Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Structural Biology

Background:

  • p21-activated kinases (PAK) are serine/threonine kinases crucial for cellular functions.
  • PAKs are downstream effectors of RHO GTPases, regulating cytoskeleton, growth, survival, and polarity.
  • PAK4 is a type II PAK implicated in various cellular processes.

Purpose of the Study:

  • To investigate the interaction between PAK4 and RHO GTPases, specifically CDC42.
  • To elucidate the structural basis and functional consequences of PAK4-CDC42 binding.

Main Methods:

  • Solution scattering (SAXS) to determine the overall organization of the PAK4-CDC42 complex.
  • X-ray crystallography to resolve the atomic details of the interaction interface.
  • Biochemical assays to assess kinase activity and binding affinity.

Main Results:

  • Full-length PAK4 forms a compact heterodimer with CDC42.
  • X-ray crystallography revealed canonical CRIB domain binding and additional interactions involving the PAK4 kinase C-lobe and polybasic region.
  • These novel interactions enhance CDC42 binding affinity and modulate PAK4 kinase activity.

Conclusions:

  • The interaction between PAK4 and CDC42 is more complex than previously understood.
  • Additional binding sites beyond the CRIB domain significantly influence PAK4's functional regulation.
  • This provides new insights into the intricate mechanisms of RHO GTPase signaling and kinase regulation.