Joachim Frank's Binding with the Ribosome

Abstract

With recent technological advancements, single-particle cryogenic electron microscopy (cryo-EM) is now the technique of choice to study structure and function of biological macromolecules at near-atomic resolution. Many single-particle EM reconstruction methods necessary for these advances were pioneered by Joachim Frank, and were optimized using the ribosome as a benchmark specimen. In doing so, he made several landmark contributions to the understanding of the structure and function of ribosomes. These include the first 3D visualization of ribosome-bound transfer RNAs, the first experimentally derived structures of the primary complexes formed during the bacterial translation elongation cycle, and the critical ribosomal conformational transitions required for translation. Over the years, his laboratory studied many important functional complexes of the ribosome from both eubacterial and eukaryotic systems, including ribosomes from pathogenic organisms. This article presents a brief account of the contributions made by Joachim Frank to the ribosome field.

Keywords: Joachim Frank's contributions; cryo-EM; ribosome structure and function.

Fig. 1.

The first three-dimensional cryo-EM reconstruction of the E. coli 70S ribosome at 40 Å resolution. The magenta meshed envelope represents the density of the ribosome, where the relatively high-density core (cyan) was depicted as the envelop of the ribosomal RNAs. Reproduced from Ref. , with permission of Journal of Cell Biology Press.

Fig. 2.

The first experimentally visualized positions of the ribosome-binding ligands to infer main sequence of events during bacterial translation elongation cycle. Positions of the tRNAs and elongation factors EF-Tu and EF-G were derived from multiple 15- 20 Å resolution cryo-EM maps of defined functional complexes. (modified from Ref 25).

Fig. 3.

Multiple conformational states observed in functional complexes of the ribosome led to the suggestion that fine tuning of rotation between the two ribosomal subunits would help recognize various translation factors by the ribosome. Reproduced from Ref. , with permission of Cold Spring Harbor Laboratory Press.

Fig. 4.

Cryo-EM map of the large ribosomal subunit of Trypanosoma cruzi at 2.5-Å resolution. The core of the subunit was resolved up to 2.3 Å, as shown by applying a cutting plane (right panel). Reproduced from Ref. , with permission of Proc Natl Acad Sci U S A Press.