Regulation of hSos1 activity is a system-level property generated by its multi-domain structure

摘要: Abstract The multi-domain protein hSos1 plays a major role in cell growth and differentiation through its Ras-specific guanine nucleotide exchange domain whose complex regulation involves intra-molecular, inter-domain rearrangements. We present stochastic mathematical model describing intra-molecular of activity. population macroscopic effect is reproduced Monte-Carlo approach. Key parameters have been experimentally determined by BIAcore analysis. Complementation experiments Saccharomyces cerevisiae cdc25 ts strain with Sos deletion mutants provided comprehensive data set for estimation unknown validation. robust against parameter alteration describes both the behavior modulation activity full length molecule under physiological conditions. By incorporating calculated aminoacid changes at an interface, mutant correlating developmental syndrome could be simulated, further validating model. activation state arises as “emergent property” structure that allows multi-level integration network intra- inter-molecular signals.