Laser phase plate improves structure determination of small proteins by cryo-EM

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Authors: Petar N. Petrov, Jessie T. Zhang, Jonathan Remis, Jeremy J. Axelrod, Hang Cheng, Eric S. Cooper, Ian K. Hicklin, Shahar Sandhaus, Cooper Schnurr, Robert M. Glaeser, Holger Mueller
Cited by: 4
References: 49

Abstract

Phase plates can, in principle, overcome the poor image contrast in cryo-electron microscopy (cryo-EM) and the resulting limits on the structural reconstruction of small proteins. However, previous designs have been unstable and compromised the high-resolution signal and have thus been unable to surpass results achieved by standard cryo-EM. Here, we show that the laser phase plate (LPP), installed in a modern, custom Titan Krios microscope, enhances the resolution in single-particle reconstruction of small proteins by improving specimen-motion correction and recovery of information from the early frames, as well as particle visualization, three-dimensional classification, and alignment. These advances use standard defocus ranges and reconstruction procedures but open the door to LPP-tailored protocols, offering further improvements by leveraging the LPP demonstrated here.

Fields of Study & Subjects

Advanced Electron Microscopy Techniques and Applications Advanced X-ray Imaging Techniques Force Microscopy Techniques and Applications

Publication details

Journal / source
Science
Publisher
American Association for the Advancement of Science (AAAS)
Volume
393
Issue
6807
Pages
195–199
Publication date
11 June 2026
Language
EN