Novel biochemical, structural, and systems insights into inflammatory signaling revealed by contextual interaction proteomics.
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ICR Authors
Authors
Ciuffa, R
Uliana, F
Mannion, J
Mehnert, M
Tenev, T
Marulli, C
Satanowski, A
Keller, LML
Rodilla RamÃrez, PN
Ori, A
Gstaiger, M
Meier, P
Aebersold, R
Uliana, F
Mannion, J
Mehnert, M
Tenev, T
Marulli, C
Satanowski, A
Keller, LML
Rodilla RamÃrez, PN
Ori, A
Gstaiger, M
Meier, P
Aebersold, R
Document Type
Journal Article
Date
2022-10-04
Date Accepted
2022-10-04
Abstract
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.
Citation
Proceedings of the National Academy of Sciences of USA, 2022, 119 (40), pp. e2117175119 -
Source Title
Proceedings of the National Academy of Sciences of USA
Publisher
NATL ACAD SCIENCES
ISSN
0027-8424
eISSN
1091-6490
1091-6490
1091-6490
Collections
Research Team
Cell Death and Immunity