Novel biochemical, structural, and systems insights into inflammatory signaling revealed by contextual interaction proteomics.
Date
2022-10-04Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
TNF-RSC
contextual proteomics
inflammatory signaling
interaction proteomics
stoichiometry
Biological Phenomena
Protein Interaction Mapping
Protein Interaction Maps
Proteome
Proteomics
Research team
Cell Death and Immunity
Language
eng
Date accepted
2022-10-04
License start date
2022-10-04
Citation
Proceedings of the National Academy of Sciences of USA, 2022, 119 (40), pp. e2117175119 -
Publisher
NATL ACAD SCIENCES
Except where otherwise noted, this item's license is described
as
http://creativecommons.org/licenses/by/4.0/
Related items
Showing items related by title, author, creator and subject.
-
Cholesterol biosynthesis pathway as a novel mechanism of resistance to estrogen deprivation in estrogen receptor-positive breast cancer.
Simigdala, N; Gao, Q; Pancholi, S; Roberg-Larsen, H; Zvelebil, M; et al. (BMC, 2016-06-01)BACKGROUND: Therapies targeting estrogenic stimulation in estrogen receptor-positive (ER+) breast cancer (BC) reduce mortality, but resistance remains a major clinical problem. Molecular studies have shown few high-frequency ... -
Systematic evaluation of quantotypic peptides for targeted analysis of the human kinome.
Worboys, JD; Sinclair, J; Yuan, Y; Jørgensen, C (NATURE PUBLISHING GROUP, 2014-10-01)In targeted proteomics it is critical that peptides are not only proteotypic but also accurately represent the level of the protein (quantotypic). Numerous approaches are used to identify proteotypic peptides, but quantotypic ... -
Proteomic research in sarcomas - current status and future opportunities.
Burns, J; Wilding, CP; L Jones, R; H Huang, P (ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2020-04-01)Sarcomas are a rare group of mesenchymal cancers comprising over 70 different histological subtypes. For the majority of these diseases, the molecular understanding of the basis of their initiation and progression remains ...