association rate constants of ras-effector interactions are evolutionarily conserved协会的速率常数ras-effector交互进化守恒的.pdfVIP

Association Rate Constants of Ras-Effector Interactions Are Evolutionarily Conserved 1 2 3 Christina Kiel *, Dorothee Aydin , Luis Serrano 1 EMBL-CRG Systems Biology Unit, Centre de Regulacio Genomica, Barcelona, Spain, 2 EMBL-European Molecular Biology Laboratory, Heidelberg, Germany, 3 ICREA Professor, EMBL-CRG Systems Biology Unit, Centre de Regulacio Genomica, Barcelona, Spain Abstract Evolutionary conservation of protein interaction properties has been shown to be a valuable indication for functional importance. Here we use homology interface modeling of 10 Ras-effector complexes by selecting ortholog proteins from 12 organisms representing the major eukaryotic branches, except plants. We find that with increasing divergence time the sequence similarity decreases with respect to the human protein, but the affinities and association rate constants are conserved as predicted by the protein design algorithm, FoldX. In parallel we have done computer simulations on a minimal network based on Ras-effector interactions, and our results indicate that in the absence of negative feedback, changes in kinetics that result in similar binding constants have strong consequences on network behavior. This, together with the previous results, suggests an important biological role, not only for equilibrium binding constants but also for kinetics in signaling processes involving Ras-effector interactions. Our findings are important to take into consideration in system biology approaches and simulations of biological networks. Citation: Kiel C, Aydin D, Serrano L (2008) Association Rate Constants of Ras-Effector Interactions Are Evolutionarily Conserved. PLoS Comput Biol 4(12): e1000245. doi:10.1371/journal.pcbi.1000245 Editor: Chri