Scientists reveal protein synthesis mechanism in Giardia

Scientists reveal protein synthesis mechanism in Giardia

Cryo-EM structure of the Giardia ribosome reveals a highly compact, GC-rich rRNA with eukaryotic r proteins. (A) Structure of the Giardia ribosome with all r proteins stained (SSU, shades of blue and green; LSU, shades of red and purple) and labeled. (B) Four views (90° related) of the Giardia (top) and Saccharomyces (bottom) ribosomes with rRNA ESs (ES for LSU, colored in red and purple; es for SSU, colored in blue and green) . ESs are similarly stained in both ribosomes for size comparison. (C) Distribution of A (blue), U (dark blue), G (orange) and C (yellow) nucleotides across the rRNA in Giardia and Saccharomyces ribosomes. (D) Percentage of A, U, G and C in Giardia and Saccharomyces ribosomes compared in a histogram. Credit: Research on nucleic acids (2023). DOI: 10.1093/nar/gkad176

Scientists at Uppsala University have used cryo-electron microscopy to reveal details of the protein synthesis mechanism in the parasite Giardia intestinalis, which causes diarrhea. The new insights could be valuable for screening specific drugs against Giardia and other unicellular parasites.

Cryo-electron microscopy (cryo-EM) is a very powerful tool that makes it possible to visualize cellular machinery at high magnification. The cryogenic setup prevents damage and deformation of the biological samples and therefore the cellular processes can be seen as a series of snapshots, but with molecular details.

Cryo-EM has played an important role in recent years in unraveling the steps of protein synthesis in various species, from bacteria to humans. Yet there was no knowledge of the protein synthesis process in protozoan organisms, a group of single-celled organisms that are often parasitic to humans and other mammals.

Uppsala scientist Professor Suparna Sanyal and her team members, especially Dr. Soneya Majumdar and Ph.D. student Andrew Emmerich, took on the challenging project in 2020 to unravel the details of the protein synthesis of Giardia intestinalis.

Giardia is an important research topic, not only because it causes nasty diarrhea in mammals, but also because it serves as a model system for much more dangerous unicellular parasites. In collaboration with Giardia expert Professor Staffan Svärd of Uppsala University, the research group grew Giardia and purified native ribosomes, which are the cell’s protein factory. They set up cryo-EM grids at the Uppsala University facility and collected cryo-EM data at the Umeå node of the SciLifeLab facility.

After two years of hard work, they were able to resolve high-resolution structures of six different states of elongation of Giardia protein synthesis. These novel structures could be assembled into a video showing sequential changes in ribosome structure, movement of the tRNAs, and the binding and release of translation elongation factor eEF2 – all essential for protein synthesis in Giardia and other protozoa.

In addition, Sanyal and colleagues were able to decipher key differences between the Giardia ribosome and bacterial and human ribosomes, which could be valuable for screening specific drugs against Giardia and other protozoan parasites.

The findings are published in the journal Research on nucleic acids.

More information:
Soneya Majumdar et al., Insights into translocation mechanism and ribosome evolution of cryo-EM structures from translocation intermediates of Giardia intestinalis, Research on nucleic acids (2023). DOI: 10.1093/nar/gkad176

Offered by the Swedish Research Council

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