The fine structure of the human ribosome unveiled!
Example of 3D elements revealed in the atomic structure of the full human ribosome (80S). The high resolution (in the Angstrom range, Å, i.e. 0.1 nanometer) allows discrimination between elements interacting or not.
Nature April 30, 2015
April 22, 2015
The team of Bruno Klaholz, at IGBMC reveals the atomic 3D structure of the full human ribosome and its fine interactions, notably between RNAs and proteins, the human’s molecular machinery catalyzing protein biosynthesis.
These outstanding findings provide unprecedented insights into the structure and the dynamics of the full human ribosome and pave the way for new major explorations like analyzing antibiotic side-effects or, in the long term, the treatment of diseases related to ribosome’s dysfunction and deregulated protein synthesis, including cancer.
These results are published April 22th, 2015 in Nature.
Ribosomes are large molecular machineries which directly intervene in gene translation and protein biosynthesis, based on the genetic code, inside any living being’s cells. The atomic structure of ribosomes is precisely known for several species, but that of the human ribosome – being exceptionally complex – was still a major challenge.
Yet, the team of Bruno Klaholz, at IGBMC, reveals an unprecedented view of the atomic structure of the full human ribosome, reaching a resolution beyond 3 Å (0,3 nanometer).
The structure was obtained from highly purified samples and a combination of image processing and near-atomic 3D reconstruction using high-resolution images from a new-generation electron cryo-microscope*, unique in France, whose outstanding performance is obtained thanks to a direct electron detector camera and spherical aberration correction.
The researchers managed to explore for the first time the arrangement of the full human ribosome, at atomic scale, and the fine molecular interactions, notably between RNA and proteins, which occur in it.
They also reveal atomic details of the subunit interface, which is seen to strongly remodel upon rotational movements of the ribosomal subunits during protein biosynthesis.
Finally, located at the subunit interface, they obtained unprecedented insights into specific molecular interactions between transfer RNA and the exit site of the ribosome.
This precise knowledge of the structure and the dynamics of the full human ribosome pave the way for new major explorations of functional complexes. It is now also possible to undertake the analysis of antibiotic side-effects as they can possibly target “by mistake” the human ribosome. It may now also become possible to consider, on the long term, applications towards the treatment of diseases related to ribosome’s dysfunction and deregulated protein synthesis, including cancer.
* Titan Krios electron cryo-microscope is a 3,40 meters tall giant operating at 300 000 volts, entirely automatized and equipped with the latest generation detector and aberration corrector. It is located at the new Center for integrative biology (CBI) of the IGBMC Institute, which gathers leading-edge technologies, platformsfor scientists and the coordination of the French infrastructure FRISBI. Inaugurated in January 2015, the CBI was made possible thanks to many partners’ support, among them FRISBI and the Alsace region.