Related Experiment Video

Updated: Apr 11, 2026

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein
07:08

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein

Published on: January 16, 2020

6.2K

GTP-Dependent K-Ras Dimerization

Serena Muratcioglu1, Tanmay S Chavan2, Benjamin C Freed3

  • 1Department of Chemical and Biological Engineering, Koc University, Rumelifeneri Yolu, 34450 Sariyer Istanbul, Turkey.

Structure (London, England : 1993)
|June 9, 2015
PubMed

Insights

Ras proteins, crucial for cell signaling, can form dimers. These Ras dimers influence the activity of downstream proteins like Raf, potentially offering new therapeutic targets for cancer treatment.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Oncology

Background:

  • Ras proteins are key regulators of receptor-initiated signal transduction pathways.
  • Activation of Raf, a critical downstream effector, necessitates its dimerization.
  • The role of Ras dimerization in promoting Raf activation has been hypothesized.

Purpose of the Study:

  • To investigate the self-association properties of the K-Ras4B catalytic domain.
  • To elucidate the structural basis of Ras dimerization and its impact on effector interactions.
  • To explore the therapeutic potential of targeting Ras dimerization in cancer.

Main Methods:

  • Biochemical and biophysical characterization of GTP-bound K-Ras4B catalytic domain.
  • Identification and analysis of Ras homodimer interfaces.
  • Structural analysis of Ras-effector binding regions.

Main Results:

  • The GTP-bound catalytic domain of K-Ras4B forms stable homodimers.
  • Two distinct dimer interfaces were identified: a β-sheet interface and a helical interface.
  • The β-sheet interface overlaps with binding sites for multiple effectors (Raf, PI3K, RalGDS) and may be inhibitory.
  • The helical interface also overlaps effector binding sites and may promote Raf activation.

Conclusions:

  • Ras self-association directly regulates effector binding and activity.
  • Ras dimers can modulate Raf signaling through distinct interfaces.
  • Targeting the helical Ras dimer interface could be a viable strategy to inhibit Raf signaling in cancer.

More Related Videos

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.6K
Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells10:27

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 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:
5.8K
The Ras Gene02:38

The Ras Gene

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...
7.5K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.4K
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,...
10.3K
GTPases and their Regulation02:14

GTPases and their Regulation

3.3K
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
21.1K