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Quantifying the heterogeneity of macromolecular machines by mass photometry

Abstract:
Sample purity is central to in vitro studies of protein function and regulation, and to the efficiency and success of structural studies using techniques such as x-ray crystallography and cryo-electron microscopy (cryo-EM). Here, we show that mass photometry (MP) can accurately characterize the heterogeneity of a sample using minimal material with high resolution within a matter of minutes. To benchmark our approach, we use negative stain electron microscopy (nsEM), a popular method for EM sample screening. We include typical workflows developed for structure determination that involve multi-step purification of a multi-subunit ubiquitin ligase and chemical cross-linking steps. When assessing the integrity and stability of large molecular complexes such as the proteasome, we detect and quantify assemblies invisible to nsEM. Our results illustrate the unique advantages of MP over current methods for rapid sample characterization, prioritization and workflow optimization.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-020-15642-w

Authors


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Role:
Author
ORCID:
0000-0002-4024-5497
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Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Physical & Theoretical Chem
Role:
Author


Publisher:
Springer Nature
Journal:
Nature Communications More from this journal
Volume:
11
Article number:
1772
Publication date:
2020-04-14
Acceptance date:
2020-03-12
DOI:
EISSN:
2041-1723
Pmid:
32286308


Language:
English
Keywords:
Subjects:
Pubs id:
1100514
Local pid:
pubs:1100514
Deposit date:
2020-05-21

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