Equilibrium and dynamical properties of protein binding networks
by
Prof.Sergei Maslov(Brookhaven National Laboratory)
→
Europe/Stockholm
F 670 (MTC, KI)
F 670
MTC, KI
Theorells väg 3
Karolinska Institutet
Description
Large-scale protein-protein interaction networks serve as a paradigm of
complex properties of living cells. These networks are naturally
weighted with edges characterized by binding strength ( association
constant) and protein-nodes – by their concentrations. However,
state-of-the-art high-throughput experimental techniques generate just a
binary (yes or no) information about individual interactions. As a
result, most of the previous research concentrated just on topology of
these networks. In a series of recent publications [1-4] my
collaborators and I went beyond purely topological studies and
calculated the mass-action equilibrium of a genome-wide binding network
using experimentally determined protein concentrations, subcellular
localizations, and reliable binding interactions in baker’s yeast. We
then studied how this equilibrium responds to large perturbations [1-2]
and stochastic noise [3] in concentrations of proteins. It was found
that the magnitude of relative changes in free (monomer) and bound
(heterodimer) concentrations of perturbed proteins exponentially decays
with network distance from the source of perturbation. This explains
why, despite a globally connected topology, individual functional
modules in such networks are able to operate fairly independently.
Another conclusion of our study is that the robustness of the
equilibrium state is determined by
1) the topological structure of the network; 2) balance of
concentrations of interacting proteins; and 3) the average binding
strength of interactions. At the same time
it only weakly depends on (current unknown) dissociation constants of
individual interactions.
In a separate study [4] we quantified the interplay between specific and
non-specific binding interactions under crowded conditions inside living
cells. We show how the need to limit the waste of resources inside
non-specific complexes constrains the number of types and concentrations
of proteins that are present at the same time and at the same
compartment of the cell.
[1.] S Maslov, I. Ispolatov, PNAS 104:13655 (2007).
[2.] S. Maslov, K. Sneppen, I. Ispolatov, New J. of Phys. 9: 273 (2007).
[3.]K-K. Yan, D. Walker, S. Maslov, Phys. Rev. Lett., 101, 268102 (2008).
[4.]J. Zhang, S. Maslov, and E. I. Shakhnovich, Mol. Syst. Biol. 4, 210
(2008).