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PreprintCited by 3Protein Structure and DynamicsEnzyme Structure and FunctionMass Spectrometry Techniques and Applications

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Protein Quaternary Structures in Solution are a Mixture of Multiple forms

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Marciano, Shir, Dey, Debabrata, Listov, Dina, Fleishman, Sarel J, Sonn-Segev, Adar, Mertens, Haydyn, Busch, Florian, Kim, Yongseok, Harvey, Sophie R., Wysocki, Vicki H., Schreiber, Gideon·2022·bioRxiv (Cold Spring Harbor Laboratory)
DOI 10.1101/2022.03.30.486392

Preprint — published as 10.1039/d2sc02794a · Paper page

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Abstract

Over half the proteins form homo or hetero-oligomeric structures. Experimentally determined structures are often considered in determining a protein’s oligomeric state, but static structures miss the dynamic equilibrium between different quaternary forms. The problem is exacerbated in homo-oligomers, where the oligomeric states are challenging to characterize. Here, we re-evaluated the oligomeric state of 17 different bacterial proteins across a broad range of protein concentrations and solutions by native mass-spectrometry (MS), mass photometry (MP), size exclusion chromatography (SEC), and small-angle x-ray scattering (SAXS), finding that most exhibit several oligomeric states. Surprisingly, many proteins did not show mass-action driven equilibrium between the oligomeric states. For approximately half the proteins, the predicted oligomeric forms described in publicly available databases underestimated the complexity of protein quaternary structures in solution. Conversely, AlphaFold Multimer provided an accurate description of the potential multimeric states for most proteins, suggesting that it could help resolve uncertainties on the solution state of many proteins.

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Metadata

Authors
Marciano, S., Dey, D., Listov, D., Fleishman, S. J., Sonn-Segev, A., Mertens, H., Busch, F., Kim, Y., Harvey, S. R., Wysocki, V. H., & Schreiber, G.
Affiliations
  • Weizmann Institute of Science (IL)
  • European Molecular Biology Laboratory (DE)
  • The Ohio State University (US)
Corresponding author
Schreiber, Gideon
ORCID
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2022-03-31
DOI
10.1101/2022.03.30.486392
OpenAlex
W4220889120
Cited by
3
References
2
Citations by year
2023: 1 · 2022: 2
Type
posted content
Language
en
Open access
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Desy publication database (The Deutsches Elektronen-Synchrotron) (submittedVersion, cc-by)
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
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
Keywords
quaternary structure, oligomeric state, bacterial proteins, homo-oligomers, hetero-oligomers, AlphaFold-Multimer, protein dynamics in solution

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