Novel biochemical, structural, and systems insights into inflammatory signaling revealed by contextual interaction proteomics
A recent PNAS paper by the Aebersold group (IMSB) in collaboration with the Meier group (ICR, London) developed a new proteomic workflow to investigate composition, absolute stoichiometry and assembly dynamics of the TNF receptor signaling complex.
Protein–protein interactions (PPIs) represent the main mode of the proteome organization in the cell. In the last decade, several large-scale representations of PPI networks have captured generic aspects of the functional organization of network components but mostly lack the context of cellular states. However, the generation of context-dependent PPI networks is essential for structural and systems-level modeling of biological processes—a goal that remains an unsolved challenge. Here we describe an experimental/computational strategy to achieve a modeling of PPIs that considers contextual information. This strategy defines the composition, stoichiometry, temporal organization, and cellular requirements for the formation of target assemblies. We used this approach to generate an integrated model of the formation principles and architecture of a large signalosome, the TNF–receptor signaling complex (TNF-RSC). Overall, we show that the integration of systems- and structure-level information provides a generic, largely unexplored link between the modular proteome and cellular function.
Link to the paper in external page PNAS