Issue 10, 2011

Towards a quantitative model of the post-synaptic proteome

Abstract

The postsynaptic compartment of the excitatory glutamatergic synapse contains hundreds of distinct polypeptides with a wide range of functions (signalling, trafficking, cell-adhesion, etc.). Structural dynamics in the post-synaptic density (PSD) are believed to underpin cognitive processes. Although functionally and morphologically diverse, PSD proteins are generally enriched with specific domains, which precisely define the mode of clustering essential for signal processing. We applied a stochastic calculus of domain binding provided by a rule-based modelling approach to formalise the highly combinatorial signalling pathway in the PSD and perform the numerical analysis of the relative distribution of protein complexes and their sizes. We specified the combinatorics of protein interactions in the PSD by rules, taking into account protein domain structure, specific domain affinity and relative protein availability. With this model we interrogated the critical conditions for the protein aggregation into large complexes and distribution of both size and composition. The presented approach extends existing qualitative protein-protein interaction maps by considering the quantitative information for stoichiometry and binding properties for the elements of the network. This results in a more realistic view of the postsynaptic proteome at the molecular level.

Graphical abstract: Towards a quantitative model of the post-synaptic proteome

Supplementary files

Article information

Article type
Paper
Submitted
20 Apr 2011
Accepted
17 Aug 2011
First published
26 Aug 2011

Mol. BioSyst., 2011,7, 2813-2823

Towards a quantitative model of the post-synaptic proteome

O. Sorokina, A. Sorokin and J. D. Armstrong, Mol. BioSyst., 2011, 7, 2813 DOI: 10.1039/C1MB05152K

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