Cryo-EM structure of the ancient eukaryotic ribosome from the human parasite Giardia lamblia.

Disha-Gajanan Hiregange, Andre Rivalta, Tanaya Bose, Elinor Breiner-Goldstein, Sarit Samiya, Giuseppe Cimicata, Liudmila Kulakova, Ella Zimmerman, Anat Bashan, Osnat Herzberg, Ada Yonath

Nucleic acids research 2022 Feb 22

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Giardiasis is a disease caused by the protist Giardia lamblia. As no human vaccines have been approved so far against it, and resistance to current drugs is spreading, new strategies for combating giardiasis need to be developed. The G. lamblia ribosome may provide a promising therapeutic target due to its distinct sequence differences from ribosomes of most eukaryotes and prokaryotes. Here, we report the cryo-electron microscopy structure of the G. lamblia (WB strain) ribosome determined at 2.75 Å resolution. The ribosomal RNA is the shortest known among eukaryotes, and lacks nearly all the eukaryote-specific ribosomal RNA expansion segments. In contrast, the ribosomal proteins are typically eukaryotic with some species-specific insertions/extensions. Most typical inter-subunit bridges are maintained except for one missing contact site. Unique structural features are located mainly at the ribosome's periphery. These may be exploited as target sites for the design of new compounds that inhibit selectively the parasite's ribosomal activity. © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

Citation

Disha-Gajanan Hiregange, Andre Rivalta, Tanaya Bose, Elinor Breiner-Goldstein, Sarit Samiya, Giuseppe Cimicata, Liudmila Kulakova, Ella Zimmerman, Anat Bashan, Osnat Herzberg, Ada Yonath. Cryo-EM structure of the ancient eukaryotic ribosome from the human parasite Giardia lamblia. Nucleic acids research. 2022 Feb 22;50(3):1770-1782