Novel biochemical, structural, and systems insights into inflammatory signaling revealed by contextual interaction proteomics.

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Authors

Ciuffa, R
Uliana, F
Mannion, J
Mehnert, M
Tenev, T
Marulli, C
Satanowski, A
Keller, LML
Rodilla Ramírez, 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

Research Team

Cell Death and Immunity

Notes