Work

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

Year: 2026

Type: article

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.

Source: Science

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 Müller

Institutions: Institute of Science and Technology Austria, University of California, Berkeley, Lawrence Berkeley National Laboratory, QB3

Language: English

Topic: Advanced Electron Microscopy Techniques and Applications

Subfield: Structural Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Gordon and Betty Moore Foundation, Chan Zuckerberg Initiative, National Institutes of Health

Awards: Investigating MHC-I downregulation by HIV-1 Nef using cryo-electron tomography with laser-based phase contrast, G5704696026, G7318442848, G9000140780

OpenAlex ID: W7164365390

FWCI: 8.412

Cites: 49

Cited by: 4

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