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Published (Version of record)CC BY V4.0, Open Access
Published (Version of record)CC BY V4.0, Open Access
Journal article
Protein quaternary structures in solution are a mixture of multiple forms
Chemical science (Cambridge), Vol.13(39), pp.11680-11695
21/Sep/2022
Abstract
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.
Details
- Title
- Protein quaternary structures in solution are a mixture of multiple forms
- Creators
- Shir Marciano - 972WIS_INST___112Debabrata Dey - 972WIS_INST___112Dina Listov - 972WIS_INST___112Sarel J Fleishman - 972WIS_INST___112Adar Sonn-SegevHaydyn Mertens - European Molecular Biology LaboratoryFlorian Busch - The Ohio State UniversityYongseok Kim - The Ohio State UniversitySophie R Harvey - The Ohio State UniversityVicki H Wysocki - The Ohio State UniversityGideon Schreiber (Corresponding Author) - 972WIS_INST___112
- Resource Type
- Journal article
- Publication Details
- Chemical science (Cambridge), Vol.13(39), pp.11680-11695; 21/Sep/2022
- Number of pages
- 16
- Language
- English
- DOI
- https://doi.org/10.1039/d2sc02794a
- Grant note
- This research was supported by the Israel Science Foundation grant no. 1268/18 (GS). The SAXS experiment at the P12 EMBL beamline at the PETRA III storage ring of DESY synchrotron, Hamburg, Germany, was supported by iNEXT project number 653706, funded by the Horizon 2020 Program of the European Union. Native mass spectrometry measurements were provided by the NIH-funded Resource for Native Mass Spectrometry Guided Structural Biology at The Ohio State University (NIH P41 GM128577, (VW)). The study was designed by SM and GS; sample preparations were made by SM, DD, YK, SH and FB. Experiments were performed by SM, SH, FB, HM and YK. Data were analyzed by SM, YK, FB, SH, VW, GS and HM. AlphaFold calculations and analysis by DL and SJF. SM, YK, FB, VW, HM, DL and GS wrote the paper. All authors read and approved the final manuscript.
- Record Identifier
- 993403495703596
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