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

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 sta...

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Autores principales: Ciuffa, Rodolfo, Uliana, Federico, Mannion, Jonathan, Mehnert, Martin, Tenev, Tencho, Marulli, Cathy, Satanowski, Ari, Keller, Lena Maria Leone, Rodilla Ramírez, Pilar Natalia, Ori, Alessandro, Gstaiger, Matthias, Meier, Pascal, Aebersold, Ruedi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546619/
https://www.ncbi.nlm.nih.gov/pubmed/36179048
http://dx.doi.org/10.1073/pnas.2117175119
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author Ciuffa, Rodolfo
Uliana, Federico
Mannion, Jonathan
Mehnert, Martin
Tenev, Tencho
Marulli, Cathy
Satanowski, Ari
Keller, Lena Maria Leone
Rodilla Ramírez, Pilar Natalia
Ori, Alessandro
Gstaiger, Matthias
Meier, Pascal
Aebersold, Ruedi
author_facet Ciuffa, Rodolfo
Uliana, Federico
Mannion, Jonathan
Mehnert, Martin
Tenev, Tencho
Marulli, Cathy
Satanowski, Ari
Keller, Lena Maria Leone
Rodilla Ramírez, Pilar Natalia
Ori, Alessandro
Gstaiger, Matthias
Meier, Pascal
Aebersold, Ruedi
author_sort Ciuffa, Rodolfo
collection PubMed
description 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.
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spelling pubmed-95466192022-10-08 Novel biochemical, structural, and systems insights into inflammatory signaling revealed by contextual interaction proteomics Ciuffa, Rodolfo Uliana, Federico Mannion, Jonathan Mehnert, Martin Tenev, Tencho Marulli, Cathy Satanowski, Ari Keller, Lena Maria Leone Rodilla Ramírez, Pilar Natalia Ori, Alessandro Gstaiger, Matthias Meier, Pascal Aebersold, Ruedi Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2022-09-30 2022-10-04 /pmc/articles/PMC9546619/ /pubmed/36179048 http://dx.doi.org/10.1073/pnas.2117175119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Ciuffa, Rodolfo
Uliana, Federico
Mannion, Jonathan
Mehnert, Martin
Tenev, Tencho
Marulli, Cathy
Satanowski, Ari
Keller, Lena Maria Leone
Rodilla Ramírez, Pilar Natalia
Ori, Alessandro
Gstaiger, Matthias
Meier, Pascal
Aebersold, Ruedi
Novel biochemical, structural, and systems insights into inflammatory signaling revealed by contextual interaction proteomics
title Novel biochemical, structural, and systems insights into inflammatory signaling revealed by contextual interaction proteomics
title_full Novel biochemical, structural, and systems insights into inflammatory signaling revealed by contextual interaction proteomics
title_fullStr Novel biochemical, structural, and systems insights into inflammatory signaling revealed by contextual interaction proteomics
title_full_unstemmed Novel biochemical, structural, and systems insights into inflammatory signaling revealed by contextual interaction proteomics
title_short Novel biochemical, structural, and systems insights into inflammatory signaling revealed by contextual interaction proteomics
title_sort novel biochemical, structural, and systems insights into inflammatory signaling revealed by contextual interaction proteomics
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546619/
https://www.ncbi.nlm.nih.gov/pubmed/36179048
http://dx.doi.org/10.1073/pnas.2117175119
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