Structure determination by cryoEM at 100 keV

Electron cryomicroscopy can, in principle, determine the structures of most biological molecules but is currently limited by access, specimen preparation difficulties, and cost. We describe a purpose-built instrument operating at 100 keV-including advances in electron optics, detection, and processi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2023-12, Vol.120 (49), p.e2312905120-e2312905120
Main Authors: McMullan, Greg, Naydenova, Katerina, Mihaylov, Daniel, Yamashita, Keitaro, Peet, Mathew J, Wilson, Hugh, Dickerson, Joshua L, Chen, Shaoxia, Cannone, Giuseppe, Lee, Yang, Hutchings, Katherine A, Gittins, Olivia, Sobhy, Mohamed A, Wells, Torquil, El-Gomati, Mohamed M, Dalby, Jason, Meffert, Matthias, Schulze-Briese, Clemens, Henderson, Richard, Russo, Christopher J
Format: Article
Language:English
Subjects:
Biological Sciences
Electron optics
Molecular structure
Optics
Physical Sciences
Specimen preparation
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Summary:Electron cryomicroscopy can, in principle, determine the structures of most biological molecules but is currently limited by access, specimen preparation difficulties, and cost. We describe a purpose-built instrument operating at 100 keV-including advances in electron optics, detection, and processing-that makes structure determination fast and simple at a fraction of current costs. The instrument attains its theoretical performance limits, allowing atomic resolution imaging of gold test specimens and biological molecular structure determination in hours. We demonstrate its capabilities by determining the structures of eleven different specimens, ranging in size from 140 kDa to 2 MDa, using a fraction of the data normally required. CryoEM with a microscope designed specifically for high-efficiency, on-the-spot imaging of biological molecules will expand structural biology to a wide range of previously intractable problems.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2312905120