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Assembly of Signaling Complexes01:30

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Updated: May 28, 2026

A High-content Imaging Workflow to Study Grb2 Signaling Complexes by Expression Cloning
10:52

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Published on: October 30, 2012

Quantifying intramolecular binding in multivalent interactions: a structure-based synergistic study on Grb2-Sos1

Anurag Sethi1, Byron Goldstein, S Gnanakaran

  • 1Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.

Plos Computational Biology
|October 25, 2011
PubMed
Summary
This summary is machine-generated.

Multivalent binding enhances protein interactions. This study reveals how growth factor receptor bound protein-2 (Grb2) and son-of-sevenless 1 (Sos1) form complexes, increasing local concentrations for efficient cellular signaling.

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Combining Chemical Cross-linking and Mass Spectrometry of Intact Protein Complexes to Study the Architecture of Multi-subunit Protein Assemblies
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Combining Chemical Cross-linking and Mass Spectrometry of Intact Protein Complexes to Study the Architecture of Multi-subunit Protein Assemblies

Published on: November 28, 2017

Area of Science:

  • Molecular biology
  • Biochemistry
  • Cell signaling

Background:

  • Multivalent protein interactions are crucial for cellular specificity and affinity.
  • Growth factor receptor bound protein-2 (Grb2) and son-of-sevenless 1 (Sos1) are key signaling proteins involved in Ras activation.
  • Grb2's SH3 domains bind to polyproline motifs on Sos1, mediating signal transduction.

Purpose of the Study:

  • To understand the multivalent interactions between Grb2 and Sos1.
  • To predict an additional binding motif in Sos1 and quantify the local concentration enhancement.
  • To determine the stoichiometry and distribution of Grb2-Sos1 complexes in cells.

Main Methods:

  • Sequence analysis and binding energy calculations to predict polyproline motifs.
  • Hybrid molecular dynamics simulations and polymer modeling to estimate local concentration.
  • Thermodynamic modeling and equilibrium constant calculations for complex stoichiometry.

Main Results:

  • A fifth polyproline motif in Sos1 was predicted, increasing binding potential to Grb2.
  • Local concentration of Sos1 motifs near Grb2 increased ~1000-fold compared to cellular concentrations.
  • Calculated equilibrium constants allowed prediction of complex distributions at physiological conditions.

Conclusions:

  • This study provides a systematic analysis combining sequence, structure, and thermodynamics.
  • The findings elucidate the stoichiometry of dominant Grb2-Sos1 complexes in the cellular environment.
  • Understanding these multivalent interactions is vital for cellular signaling pathways.