The social and structural architecture of the yeast protein interactome

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The social and structural architecture of the yeast protein interactome. / Michaelis, André C; Brunner, Andreas-David; Zwiebel, Maximilian; Meier, Florian; Strauss, Maximilian T; Bludau, Isabell; Mann, Matthias.

In: Nature, Vol. 624, No. 7990, 2023, p. 192-200.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Michaelis, AC, Brunner, A-D, Zwiebel, M, Meier, F, Strauss, MT, Bludau, I & Mann, M 2023, 'The social and structural architecture of the yeast protein interactome', Nature, vol. 624, no. 7990, pp. 192-200. https://doi.org/10.1038/s41586-023-06739-5

APA

Michaelis, A. C., Brunner, A-D., Zwiebel, M., Meier, F., Strauss, M. T., Bludau, I., & Mann, M. (2023). The social and structural architecture of the yeast protein interactome. Nature, 624(7990), 192-200. https://doi.org/10.1038/s41586-023-06739-5

Vancouver

Michaelis AC, Brunner A-D, Zwiebel M, Meier F, Strauss MT, Bludau I et al. The social and structural architecture of the yeast protein interactome. Nature. 2023;624(7990):192-200. https://doi.org/10.1038/s41586-023-06739-5

Author

Michaelis, André C ; Brunner, Andreas-David ; Zwiebel, Maximilian ; Meier, Florian ; Strauss, Maximilian T ; Bludau, Isabell ; Mann, Matthias. / The social and structural architecture of the yeast protein interactome. In: Nature. 2023 ; Vol. 624, No. 7990. pp. 192-200.

Bibtex

@article{1f69068cd42e43f0bf6fdcd8373d1571,
title = "The social and structural architecture of the yeast protein interactome",
abstract = "Cellular functions are mediated by protein-protein interactions, and mapping the interactome provides fundamental insights into biological systems. Affinity purification coupled to mass spectrometry is an ideal tool for such mapping, but it has been difficult to identify low copy number complexes, membrane complexes and complexes that are disrupted by protein tagging. As a result, our current knowledge of the interactome is far from complete, and assessing the reliability of reported interactions is challenging. Here we develop a sensitive high-throughput method using highly reproducible affinity enrichment coupled to mass spectrometry combined with a quantitative two-dimensional analysis strategy to comprehensively map the interactome of Saccharomyces cerevisiae. Thousand-fold reduced volumes in 96-well format enabled replicate analysis of the endogenous GFP-tagged library covering the entire expressed yeast proteome1. The 4,159 pull-downs generated a highly structured network of 3,927 proteins connected by 31,004 interactions, doubling the number of proteins and tripling the number of reliable interactions compared with existing interactome maps2. This includes very-low-abundance epigenetic complexes, organellar membrane complexes and non-taggable complexes inferred by abundance correlation. This nearly saturated interactome reveals that the vast majority of yeast proteins are highly connected, with an average of 16 interactors. Similar to social networks between humans, the average shortest distance between proteins is 4.2 interactions. AlphaFold-Multimer provided novel insights into the functional roles of previously uncharacterized proteins in complexes. Our web portal ( www.yeast-interactome.org ) enables extensive exploration of the interactome dataset.",
keywords = "Mass Spectrometry, Protein Interaction Mapping/methods, Proteome/chemistry, Reproducibility of Results, Saccharomyces cerevisiae/chemistry, Protein Interaction Maps, Saccharomyces cerevisiae Proteins/chemistry, Epigenesis, Genetic, Databases, Factual",
author = "Michaelis, {Andr{\'e} C} and Andreas-David Brunner and Maximilian Zwiebel and Florian Meier and Strauss, {Maximilian T} and Isabell Bludau and Matthias Mann",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
doi = "10.1038/s41586-023-06739-5",
language = "English",
volume = "624",
pages = "192--200",
journal = "Nature",
issn = "0028-0836",
publisher = "nature publishing group",
number = "7990",

}

RIS

TY - JOUR

T1 - The social and structural architecture of the yeast protein interactome

AU - Michaelis, André C

AU - Brunner, Andreas-David

AU - Zwiebel, Maximilian

AU - Meier, Florian

AU - Strauss, Maximilian T

AU - Bludau, Isabell

AU - Mann, Matthias

N1 - © 2023. The Author(s).

PY - 2023

Y1 - 2023

N2 - Cellular functions are mediated by protein-protein interactions, and mapping the interactome provides fundamental insights into biological systems. Affinity purification coupled to mass spectrometry is an ideal tool for such mapping, but it has been difficult to identify low copy number complexes, membrane complexes and complexes that are disrupted by protein tagging. As a result, our current knowledge of the interactome is far from complete, and assessing the reliability of reported interactions is challenging. Here we develop a sensitive high-throughput method using highly reproducible affinity enrichment coupled to mass spectrometry combined with a quantitative two-dimensional analysis strategy to comprehensively map the interactome of Saccharomyces cerevisiae. Thousand-fold reduced volumes in 96-well format enabled replicate analysis of the endogenous GFP-tagged library covering the entire expressed yeast proteome1. The 4,159 pull-downs generated a highly structured network of 3,927 proteins connected by 31,004 interactions, doubling the number of proteins and tripling the number of reliable interactions compared with existing interactome maps2. This includes very-low-abundance epigenetic complexes, organellar membrane complexes and non-taggable complexes inferred by abundance correlation. This nearly saturated interactome reveals that the vast majority of yeast proteins are highly connected, with an average of 16 interactors. Similar to social networks between humans, the average shortest distance between proteins is 4.2 interactions. AlphaFold-Multimer provided novel insights into the functional roles of previously uncharacterized proteins in complexes. Our web portal ( www.yeast-interactome.org ) enables extensive exploration of the interactome dataset.

AB - Cellular functions are mediated by protein-protein interactions, and mapping the interactome provides fundamental insights into biological systems. Affinity purification coupled to mass spectrometry is an ideal tool for such mapping, but it has been difficult to identify low copy number complexes, membrane complexes and complexes that are disrupted by protein tagging. As a result, our current knowledge of the interactome is far from complete, and assessing the reliability of reported interactions is challenging. Here we develop a sensitive high-throughput method using highly reproducible affinity enrichment coupled to mass spectrometry combined with a quantitative two-dimensional analysis strategy to comprehensively map the interactome of Saccharomyces cerevisiae. Thousand-fold reduced volumes in 96-well format enabled replicate analysis of the endogenous GFP-tagged library covering the entire expressed yeast proteome1. The 4,159 pull-downs generated a highly structured network of 3,927 proteins connected by 31,004 interactions, doubling the number of proteins and tripling the number of reliable interactions compared with existing interactome maps2. This includes very-low-abundance epigenetic complexes, organellar membrane complexes and non-taggable complexes inferred by abundance correlation. This nearly saturated interactome reveals that the vast majority of yeast proteins are highly connected, with an average of 16 interactors. Similar to social networks between humans, the average shortest distance between proteins is 4.2 interactions. AlphaFold-Multimer provided novel insights into the functional roles of previously uncharacterized proteins in complexes. Our web portal ( www.yeast-interactome.org ) enables extensive exploration of the interactome dataset.

KW - Mass Spectrometry

KW - Protein Interaction Mapping/methods

KW - Proteome/chemistry

KW - Reproducibility of Results

KW - Saccharomyces cerevisiae/chemistry

KW - Protein Interaction Maps

KW - Saccharomyces cerevisiae Proteins/chemistry

KW - Epigenesis, Genetic

KW - Databases, Factual

U2 - 10.1038/s41586-023-06739-5

DO - 10.1038/s41586-023-06739-5

M3 - Journal article

C2 - 37968396

VL - 624

SP - 192

EP - 200

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7990

ER -

ID: 378869547