Evidence map›Paper›PMID 39277607›Full record

ArticleNature communications2024

Low-dose cryo-electron ptychography of proteins at sub-nanometer resolution.

Berk Küçükoğlu, Inayathulla Mohammed, Ricardo C Guerrero-Ferreira, Stephanie M Ribet, Georgios Varnavides, Max Leo Leidl, Kelvin Lau, Sergey Nazarov, Alexander Myasnikov, Massimo Kube and 5 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed.

  1. FPGA-based scanner and SerialEM server for 4D-STEM electron tomography.Acta crystallographica. Section D, Structural biology · 2026
    Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
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  10. Microsecond Time-Resolved Cryo-EM Based on Jet Vitrification.bioRxiv : the preprint server for biology · 2025
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Extending the reach of single-particle cryoEM.Current opinion in structural biology · 2025
    Review
  19. Review
  20. Ptychography at all wavelengths.Nature reviews. Methods primers · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Berk KüçükoğluLaboratory of Biological Electron Microscopy, Institute of Physics, School of Basic Sciences, EPFL, and Department of Fundamental Microbiology, Faculty of Biology and Medicine, UNIL, Rte. de la Sorge, 1015, Lausanne, Switzerland.
Inayathulla MohammedLaboratory of Biological Electron Microscopy, Institute of Physics, School of Basic Sciences, EPFL, and Department of Fundamental Microbiology, Faculty of Biology and Medicine, UNIL, Rte. de la Sorge, 1015, Lausanne, Switzerland.
Ricardo C Guerrero-FerreiraLaboratory of Biological Electron Microscopy, Institute of Physics, School of Basic Sciences, EPFL, and Department of Fundamental Microbiology, Faculty of Biology and Medicine, UNIL, Rte. de la Sorge, 1015, Lausanne, Switzerland.ORCID 0000-0002-3664-8277
Stephanie M RibetNational Center for Electron Microscopy (NCEM), Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
Georgios VarnavidesNational Center for Electron Microscopy (NCEM), Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.ORCID 0000-0001-8338-3323
Max Leo LeidlErnst Ruska-Centre for Microscopy and Spectroscopy with Electrons (ER-C-3): Structural Biology, Jülich, Germany.ORCID 0000-0001-8896-1647
Kelvin LauProtein Production and Structure Core Facility (PTPSP), School of Life Sciences, EPFL, Rte Cantonale, 1015, Lausanne, Switzerland.ORCID 0000-0002-9040-7597
Sergey NazarovDubochet Center for Imaging Lausanne, EPFL and UNIL, EPFL VPA DCI-Lausanne, 1015, Lausanne, Switzerland.
Alexander MyasnikovDubochet Center for Imaging Lausanne, EPFL and UNIL, EPFL VPA DCI-Lausanne, 1015, Lausanne, Switzerland.ORCID 0000-0003-2607-7121
Massimo KubeLaboratory of Biological Electron Microscopy, Institute of Physics, School of Basic Sciences, EPFL, and Department of Fundamental Microbiology, Faculty of Biology and Medicine, UNIL, Rte. de la Sorge, 1015, Lausanne, Switzerland.
Julika RadeckeLaboratory of Biological Electron Microscopy, Institute of Physics, School of Basic Sciences, EPFL, and Department of Fundamental Microbiology, Faculty of Biology and Medicine, UNIL, Rte. de la Sorge, 1015, Lausanne, Switzerland.
Carsten SachseErnst Ruska-Centre for Microscopy and Spectroscopy with Electrons (ER-C-3): Structural Biology, Jülich, Germany.ORCID 0000-0002-1168-5143
Knut Müller-CasparyDepartment of Chemistry and Centre for NanoScience, Ludwig-Maximilians-Universität München, Butenandstr. 11, 81377, München, Germany.ORCID 0000-0002-2588-7993
Colin OphusNational Center for Electron Microscopy (NCEM), Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.ORCID 0000-0003-2348-8558
Henning StahlbergLaboratory of Biological Electron Microscopy, Institute of Physics, School of Basic Sciences, EPFL, and Department of Fundamental Microbiology, Faculty of Biology and Medicine, UNIL, Rte. de la Sorge, 1015, Lausanne, Switzerland. henning.stahlberg@epfl.ch.ORCID 0000-0002-1185-4592

Funding

DOE | Advanced Research Projects Agency - Energy (Advanced Research Projects Agency - Energy - U.S. Department of Energy) DE-AC02-05CH11231EC | EU Framework Programme for Research and Innovation H2020 | H2020 European Institute of Innovation and Technology (H2020 The European Institute of Innovation and Technology) 101118656Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 200021_200628
6 · The paper itself

Abstract

Cryo-transmission electron microscopy (cryo-EM) of frozen hydrated specimens is an efficient method for the structural analysis of purified biological molecules. However, cryo-EM and cryo-electron tomography are limited by the low signal-to-noise ratio (SNR) of recorded images, making detection of smaller particles challenging. For dose-resilient samples often studied in the physical sciences, electron ptychography - a coherent diffractive imaging technique using 4D scanning transmission electron microscopy (4D-STEM) - has recently demonstrated excellent SNR and resolution down to tens of picometers for thin specimens imaged at room temperature. Here we apply 4D-STEM and ptychographic data analysis to frozen hydrated proteins, reaching sub-nanometer resolution 3D reconstructions. We employ low-dose cryo-EM with an aberration-corrected, convergent electron beam to collect 4D-STEM data for our reconstructions. The high frame rate of the electron detector allows us to record large datasets of electron diffraction patterns with substantial overlaps between the interaction volumes of adjacent scan positions, from which the scattering potentials of the samples are iteratively reconstructed. The reconstructed micrographs show strong SNR enabling the reconstruction of the structure of apoferritin protein at up to 5.8 Å resolution. We also show structural analysis of the Phi92 capsid and sheath, tobacco mosaic virus, and bacteriorhodopsin at slightly lower resolutions.

Indexed as

Cryoelectron MicroscopyProteinsApoferritinsBacteriophagesCapsidApoferritinsProteins

Identifiers

PMID39277607
PMCPMC11401879

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.