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Published on: July 17, 2019
Association rate constants of ras-effector interactions are evolutionarily conserved.
Christina Kiel1, Dorothee Aydin, Luis Serrano
1EMBL-CRG Systems Biology Unit, Centre de Regulacio Genomica, Barcelona, Spain. christina.kiel@crg.es
Plos Computational Biology
|December 20, 2008
Summary
Protein interaction properties are evolutionarily conserved, suggesting functional importance. This study shows that Ras-effector binding kinetics and affinities remain stable over evolutionary time, impacting biological network behavior.
Area of Science:
- Molecular Biology
- Systems Biology
- Evolutionary Biology
Background:
- Evolutionary conservation of protein interactions indicates functional significance.
- Ras-effector interactions are crucial in cellular signaling pathways.
Purpose of the Study:
- To investigate the evolutionary conservation of Ras-effector protein interaction properties.
- To assess the impact of conserved binding kinetics on biological network behavior.
Main Methods:
- Homology interface modeling of 10 Ras-effector complexes using orthologs from 12 eukaryotic organisms.
- Utilizing the FoldX protein design algorithm to predict binding affinities and association rate constants.
- Computer simulations of a minimal network based on Ras-effector interactions.
Main Results:
- Sequence similarity to human proteins decreases with evolutionary divergence.
- Binding affinities and association rate constants are conserved despite decreasing sequence similarity.
- Altered kinetics, even with conserved binding constants, significantly impact network dynamics in the absence of negative feedback.
Conclusions:
- Both equilibrium binding constants and kinetics play critical roles in Ras-effector signaling.
- Findings are crucial for systems biology approaches and simulations of biological networks.
- Evolutionary conservation of protein interaction kinetics highlights their functional importance in signaling.
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