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Cited by 61Advanced Electron Microscopy Techniques and ApplicationsEnzyme Structure and FunctionProtein Structure and Dynamics

Cryo-EM and artificial intelligence visualize endogenous protein community members

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Skalidis, Ioannis, Kyrilis, Fotis L., Tüting, Christian, Hamdi, Farzad, Chojnowski, Grzegorz, Kastritis, Panagiotis L.·2022·Structure
DOI 10.1016/j.str.2022.01.001
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Abstract

Cellular function is underlined by megadalton assemblies organizing in proximity, forming communities. Metabolons are protein communities involving metabolic pathways such as protein, fatty acid, and thioesters of coenzyme-A synthesis. Metabolons are highly heterogeneous due to their function, making their analysis particularly challenging. Here, we simultaneously characterize metabolon-embedded architectures of a 60S pre-ribosome, fatty acid synthase, and pyruvate/oxoglutarate dehydrogenase complex E2 cores de novo. Cryo-electron microscopy (cryo-EM) 3D reconstructions are resolved at 3.84-4.52 Å resolution by collecting <3,000 micrographs of a single cellular fraction. After combining cryo-EM with artificial intelligence-based atomic modeling and de novo sequence identification methods, at this resolution range, polypeptide hydrogen bonding patterns are discernible. Residing molecular components resemble their purified counterparts from other eukaryotes but also exhibit substantial conformational variation with potential functional implications. Our results propose an integrated tool, boosted by machine learning, that opens doors for structural systems biology spearheaded by cryo-EM characterization of native cell extracts.

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Cited by

Sorted by citations

Authors
Skalidis, I., Kyrilis, F. L., Tüting, C., Hamdi, F., Chojnowski, G., & Kastritis, P. L.
Affiliations
  • Martin Luther University Halle-Wittenberg (DE)
  • European Molecular Biology Laboratory (DE)
Corresponding author
Kastritis, Panagiotis L.
ORCID
Venue
Structure
Publisher
Elsevier BV
Published
2022-04
Volume
30
Issue
4
Pages
575-589.e6
ISSN
0969-2126 (ISSN-L)
DOI
10.1016/j.str.2022.01.001
OpenAlex
W4210742541
Cited by
61
References
7
Citations by year
2026: 15 · 2025: 10 · 2024: 12 · 2023: 14 · 2022: 10
FWCI
5.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Structure (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digitalen Hochschulbibliothek Sachsen-Anhalt (Universitäts- und Landesbibliothek Sachsen-Anhalt) (cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
metabolon, fatty acid synthase, coenzyme A synthesis, conformational heterogeneity
MeSH terms
Artificial Intelligence, Proteins, Ribosomes, Cryoelectron Microscopy

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