Protein quaternary structures in solution are a mixture of multiple forms


Over half the proteins in the E. coli cytoplasm 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, some 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.

Graphical abstract: Protein quaternary structures in solution are a mixture of multiple forms

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Article type
Edge Article
18 May 2022
21 Sep 2022
First published
21 Sep 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2022, Advance Article

Protein quaternary structures in solution are a mixture of multiple forms

S. Marciano, D. Dey, D. Listov, S. J. Fleishman, A. Sonn-Segev, H. Mertens, F. Busch, Y. Kim, S. R. Harvey, V. H. Wysocki and G. Schreiber, Chem. Sci., 2022, Advance Article , DOI: 10.1039/D2SC02794A

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