Imaging proteins at the single-molecule level
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Significance: We report a method to image and reveal structural details of proteins on a truly single-molecule level. Low-energy electron holography is used to image individual proteins electrospray deposited on freestanding graphene. In contrast to the current state of the art in structural biology, we do away with the need for averaging over many molecules. This is crucial because proteins are flexible objects that can assume distinct conformations often associated with different functions. Proteins are also the targets of almost all the currently known and available drugs. The design of new and more effective drugs relies on the knowledge of the targeted proteins structure in all its biologically significant conformations at the best possible resolution.
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Soft-landing experiments followed by electron microscopy imaging demonstrated preservation of native-like structures throughout ionisation, dehydration, and soft-landing.
“Subsequent electron microscopy (EM) imaging then demonstrated preservation of native-like structures throughout the process of ionisation, dehydration, and soft-landing.”
From Higher-order structural characterisation of native proteins and complexes by top-down mass spectrometry (2020) · cites this paper as [28]
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Zhou, M., Lantz, C., Brown, K. A., Ge, Y., Paša-Tolić, L., Loo, J. A., & Lermyte, F. (2020) · Chemical Science · doi:10.1039/d0sc04392c · Cited by 146 · see citing works
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- Authors
- Longchamp, J.-N., Rauschenbach, S., Abb, S., Escher, C., Latychevskaia, T., Kern, K., & Fink, H.-W.
- Affiliations
- University of Zurich (CH)
- Max Planck Institute for Solid State Research (DE)
- Corresponding author
- Longchamp, Jean-Nicolas
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-01-13
- Volume
- 114
- Issue
- 7
- Pages
- 1474-1479
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5321008
- OpenAlex
- W2346228447
- Cited by
- 119
- References
- 81
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 12 · 2023: 11 · 2022: 12 · 2021: 11 · 2020: 16 · 2019: 12 · 2018: 15 · 2017: 11 · 2016: 1
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- arXiv (Cornell University)
- Funders
- Swiss National Science Foundation (PZ00P2_148084, 200021_150049)
- European Commission (28326)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Electron and X-Ray Spectroscopy Techniques
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
- Keywords
- protein conformation, protein complexes, cytochrome c, bovine serum albumin, hemoglobin, free-standing graphene, sub-nanometer resolution
- MeSH terms
- Single Molecule Imaging, Animals, Cattle, Electrons, Graphite, Hemoglobins, Holography, Proteins, Serum Albumin, Bovine, Vacuum, Spectrometry, Mass, Electrospray Ionization, Cytochromes c, Static Electricity
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