Laser phase plate improves structure determination of small proteins by cryo-EM Petrov, Petar N Zhang, Jessie T. Remis, Jonathan Axelrod, Jeremy J. Cheng, Hang Cooper, Eric S. Hicklin, Ian K. Sandhaus, Shahar Schnurr, Cooper Glaeser, Robert M. Müller, Holger ddc:570 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. AAAS 2026 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/22365 Petrov PN, Zhang JT, Remis J, et al. Laser phase plate improves structure determination of small proteins by cryo-EM. <i>Science</i>. 2026;393(6807):195-196. doi:<a href="https://doi.org/10.1126/science.aeh0665">10.1126/science.aeh0665</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1126/science.aeh0665 info:eu-repo/semantics/altIdentifier/issn/0036-8075 info:eu-repo/semantics/altIdentifier/e-issn/1095-9203 info:eu-repo/semantics/altIdentifier/pmid/42275466 info:eu-repo/semantics/closedAccess