Research Article

Evolutionary shift toward protein-based architecture in trypanosomal mitochondrial ribosomes

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Science  26 Oct 2018:
Vol. 362, Issue 6413, eaau7735
DOI: 10.1126/science.aau7735

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Structure of the largest, most complex ribosome

Ribosomes are two-subunit ribonucleoprotein assemblies that catalyze the translation of messenger RNA into protein. Ribosomal RNAs (rRNAs) play key structural and functional roles. Ramrath et al. report the high-resolution structure of mitochondrial ribosomes from the unicellular parasite Trypanosoma brucei that contain the smallest known rRNAs. The trypanosomal mitoribosome is the most complex ribosomal assembly characterized, with two rRNAs and 126 proteins. The increased protein subunits have substituted for rRNA as an architectural scaffold. The structure also reveals the minimal core needed for ribosome function.

Science, this issue p. eaau7735

Structured Abstract


Ribosomes are universally conserved assemblies composed of ribosomal RNA (rRNA) and proteins, where rRNA plays key structural and functional roles. Despite their high degree of conservation, considerable variability is observed in mitochondrial ribosomes (mitoribosomes), with an extreme example found in Trypanosoma brucei, the parasite that causes sleeping sickness. In these mitoribosomes featuring the smallest known rRNAs, the severe rRNA reduction is accompanied by the recruitment of many additional proteins.


The extreme differences in rRNA size and the substitution of many proteins present in all other ribosomes render trypanosomal mitoribosomes an excellent system to reveal the minimal set of rRNA and protein elements essential for ribosomal function and to investigate how ribosomal proteins compensated for the missing rRNA. To address these questions, we determined the atomic structure of the mitoribosome from T. brucei using cryo–electron microscopy.


The trypanosomal mitoribosome, composed of 127 ribosomal proteins and two rRNAs, is larger and architecturally more complex than any other ribosome described so far with a molecular weight of 4.5 MDa and a RNA/protein ratio of 1:6. The structural changes are most prominent in the small subunit that exceeds the size of the “large” subunit. Notably, the reduced rRNA is found at the core of the assembly and is encased in a large shell of mitoribosomal proteins. The universally conserved regions are reduced to a minimum and include only a few rRNA and protein elements in the vicinity of key functional regions of the ribosome, namely, the decoding center, the active site, and the binding region for translation factors.

In contrast to other ribosomes, where the rRNA fold is dominated by a base-paired structure, the proteins take over the architectural role by providing a scaffold for binding of predominantly single-stranded rRNA. The switch to the protein-based architecture is accompanied by a marked increase in the size of conserved ribosomal proteins and the recruitment of novel proteins, including proteins with multiple domains or proteins with homology to various enzymes. Because many proteins contain helical repeat motifs, the assembly contains a disproportionately large fraction of α-helical elements that structurally substitute the reduced rRNA.

Our results show that, because of the extensive remodeling, the trypanosomal translational machinery adopted unusual solutions to accomplish some basic protein synthesis mechanisms. Their nascent polypeptide exit tunnel branches into two exits providing for an interesting possibility that nascent proteins with different characteristics may take different paths. Furthermore, in a subpopulation of isolated small-subunit particles, we observed mitochondrial initiation factor 3 interacting with the decoding center via its unique C-terminal extension, which might compensate for the essential function of initiation factor 1 that is absent in all mitochondria.


The unusual architecture and composition of the trypanosomal mitoribosome that we have revealed shows how proteins have taken over a key architectural role from rRNA by forming an autonomous outer shell that serves as a mold for binding flexible single-stranded rRNAs. Moreover, our results show the universally conserved features of ribosomes that are responsible for the most basic functions. Last, structural information on these ribosomes may be helpful for developing new drugs to treat sleeping sickness and other diseases caused by trypanosomes and its relatives.

The universally conserved core of the ribosome.

In the highly remodeled trypanosomal mitoribosome, where the “small” subunit is larger than the large subunit, proteins took over the key architectural role from the rRNA. The massive protein shell interacts with the extremely reduced rRNA to position functionally critical rRNA elements. The structure helps us define the “minimal” set of conserved rRNA regions and protein components shared by all ribosomes.


Ribosomal RNA (rRNA) plays key functional and architectural roles in ribosomes. Using electron microscopy, we determined the atomic structure of a highly divergent ribosome found in mitochondria of Trypanosoma brucei, a unicellular parasite that causes sleeping sickness in humans. The trypanosomal mitoribosome features the smallest rRNAs and contains more proteins than all known ribosomes. The structure shows how the proteins have taken over the role of architectural scaffold from the rRNA: They form an autonomous outer shell that surrounds the entire particle and stabilizes and positions the functionally important regions of the rRNA. Our results also reveal the “minimal” set of conserved rRNA and protein components shared by all ribosomes that help us define the most essential functional elements.

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