Novel Imaging Technique Reveals Intricate Ribosome Movements in Cells

A novel imaging method developed at HHMI's Janelia Research Campus is shedding new light on the intricate molecular processes within cells. The technique, called high-resolution template matching (HRTM), has enabled researchers to observe the movement of ribosomes in unprecedented detail.

Led by Jennifer Lippincott-Schwartz, the team used HRTM to capture ribosomes in 41 different conformational states during the protein synthesis process known as elongation. This comprehensive view allowed the creation of a 3D movie showcasing the ribosome's motion throughout the elongation cycle.

"What we are seeing is the motion of the ribosome and its binding partners at near atomic detail," explains Lippincott-Schwartz, senior author of the study published in Molecular Cell.

HRTM, developed in 2017 by Peter Rickgauer and colleagues, overcomes limitations of existing imaging techniques. While previous methods could only capture a handful of ribosome conformations, HRTM provides a more complete picture. Rickgauer, who led the new research, notes, "It's like you have every tenth page of the flipbook."

The technique uses electron microscopy images of frozen cells and employs computer simulations to detect molecular features in 2D images. By piecing together these matches, researchers constructed a seamless 3D movie of ribosome movement during elongation.

This detailed visualization revealed previously unseen movements, such as the bending motion of inter-subunit bridge proteins and the spring-like transitions of tRNA between ribosome-binding sites. These observations offer new insights into the molecular mechanisms underlying elongation.

Beyond ribosomes, HRTM shows promise for studying other molecular movements and interactions within cells. Lippincott-Schwartz concludes, "I think this is really exciting because it provides a roadmap for studying the structural dynamics of a variety of molecular complexes in cells."