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PreprintCited by 144Protein Structure and DynamicsEnzyme Structure and FunctionMachine Learning in Bioinformatics

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An atlas of protein homo-oligomerization across domains of life

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Schweke, Hugo, Levin, Tal, Pacesa, Martin, Goverde, Casper A., Kumar, Prasun, Duhoo, Yoan, Dornfeld, Lars J., Dubreuil, Benjamin, Georgeon, Sandrine, Ovchinnikov, Sergey, Woolfson, Derek N., Correia, Bruno E., Dey, Sucharita, Levy, Emmanuel D.·2023·Cell
DOI 10.1101/2023.06.09.544317

Preprint — published as 10.1016/j.cell.2024.01.022 · Paper page

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Abstract

Protein structures are essential to understand cellular processes in molecular detail. While advances in AI revealed the tertiary structure of proteins at scale, their quaternary structure remains mostly unknown. Here, we describe a scalable strategy based on AlphaFold2 to predict homo-oligomeric assemblies across four proteomes spanning the tree of life. We find that 50% of archaeal, 45% of bacterial, and 20% of eukaryotic proteomes form homomers. Our predictions accurately capture protein homo-oligomerization, recapitulate megadalton complexes, and unveil hundreds of novel homo-oligomer types. Analyzing these datasets reveals coiled-coil regions as major enablers of quaternary structure evolution in Eukaryotes. Integrating these structures with omics data shows that a majority of known protein complexes are symmetric. Finally, these datasets provide a structural context for interpreting disease mutations, which we find enriched at interfaces. Our strategy is applicable to any organism and provides a comprehensive view of homo-oligomerization in proteomes, protein networks, and disease. Abstract Figure:

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Metadata

Authors
Schweke, H., Levin, T., Pacesa, M., Goverde, C. A., Kumar, P., Duhoo, Y., Dornfeld, L. J., Dubreuil, B., Georgeon, S., Ovchinnikov, S., Woolfson, D. N., Correia, B. E., Dey, S., & Levy, E. D.
Affiliations
  • Weizmann Institute of Science (IL)
  • SIB Swiss Institute of Bioinformatics (CH)
  • University of Bristol (GB)
  • École Polytechnique Fédérale de Lausanne (CH)
  • Indian Institute of Technology Jodhpur (IN)
Corresponding author
  • Woolfson, Derek N.
  • Correia, Bruno E.
  • Dey, Sucharita
  • Levy, Emmanuel D.
ORCID
Venue
Cell
Publisher
openRxiv
Published
2023-06-11
Volume
187
Issue
4
Pages
999-1010.e15
ISSN
0092-8674 (ISSN-L)
DOI
10.1101/2023.06.09.544317
OpenAlex
W4391563878
Cited by
144
References
1
Citations by year
2026: 43 · 2025: 57 · 2024: 38 · 2023: 6
FWCI
18.82
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cell (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion, cc-by)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
  • Explore Bristol Research (submittedVersion, cc-by)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • National Science Foundation
  • Amgen
  • European Commission (HORIZON2020, 819318)
  • Human Frontier Science Program (RGP0016/2022)
  • Department of Biotechnology, Ministry of Science and Technology, India (BT/ RLF/Re-entry/10/2020)
  • École Polytechnique Fédérale de Lausanne
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • Weizmann Institute of Science
  • Israel Science Foundation (1452/18)
  • Krebsliga Schweiz (KFS-5032-02-2020)
  • Université de Genève
  • Université de Lausanne
  • Abisch-Frenkel-Stiftung
  • Peter und Traudl Engelhorn Stiftung
  • National Center of Competence in Research Chemical Biology
  • Directorate for Biological Sciences
  • Horizon 2020 Framework Programme
  • Engineering and Physical Sciences Research Council ((BB/L01386X/1), BB/L01386X, L01386X)
  • Biotechnology and Biological Sciences Research Council (BB/L01386X/1, BB/L01386X, BB/R00661X/1, L01386X)
  • European Research Council
  • Horizon 2020 (819318)
  • BrisSynBio (BB/L01386X/1)
  • NCCR Catalysis
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
Keywords
quaternary structure prediction, AlphaFold2, protein complexes, archaeal proteome, bacterial proteome, eukaryotic proteomes, protein symmetry, coiled-coil domain, pathogenic variants
MeSH terms
Archaea, Artificial Intelligence, Bacteria, Humans, Proteins, Proteome, Eukaryota

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