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

P Petar N. Petrov (Department of Physics, University of California, Berkeley, Berkeley, CA, USA.) J Jessie T. Zhang (Department of Physics, University of California, Berkeley, Berkeley, CA, USA.) J Jonathan Remis (Department of Physics, University of California, Berkeley, Berkeley, CA, USA.) J Jeremy J. Axelrod (Department of Physics, University of California, Berkeley, Berkeley, CA, USA.) H Hang Cheng (Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.) E Eric S. Cooper (Department of Physics, University of California, Berkeley, Berkeley, CA, USA.) I Ian K. Hicklin (Department of Physics, University of California, Berkeley, Berkeley, CA, USA.) S Shahar Sandhaus (Department of Physics, University of California, Berkeley, Berkeley, CA, USA.) C Cooper Schnurr (Department of Physics, University of California, Berkeley, Berkeley, CA, USA.) R Robert M. Glaeser (Lawrence Berkeley National Laboratory, Berkeley, CA, USA.) H Holger Müller (Department of Physics, University of California, Berkeley, Berkeley, CA, USA.)

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.

Article Details

Journal Science
Volume / Issue Vol. 393, Issue 6807
Published July 09, 2026
Pages 195-199
ISSN 0036-8075
Publisher American Association for the Advancement of Science

Journal Info

Science

American Association for the Advancement of Science

ISSN: 0036-8075 Social Sciences

Authors (11)

P

Petar N. Petrov

Department of Physics, University of California, Berkeley, Berkeley, CA, USA.

J

Jessie T. Zhang

Department of Physics, University of California, Berkeley, Berkeley, CA, USA.

J

Jonathan Remis

Department of Physics, University of California, Berkeley, Berkeley, CA, USA.

J

Jeremy J. Axelrod

Department of Physics, University of California, Berkeley, Berkeley, CA, USA.

H

Hang Cheng

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.

E

Eric S. Cooper

Department of Physics, University of California, Berkeley, Berkeley, CA, USA.

I

Ian K. Hicklin

Department of Physics, University of California, Berkeley, Berkeley, CA, USA.

S

Shahar Sandhaus

Department of Physics, University of California, Berkeley, Berkeley, CA, USA.

C

Cooper Schnurr

Department of Physics, University of California, Berkeley, Berkeley, CA, USA.

R

Robert M. Glaeser

Lawrence Berkeley National Laboratory, Berkeley, CA, USA.

H

Holger Müller

Department of Physics, University of California, Berkeley, Berkeley, CA, USA.