Structure of the human 80S ribosome


Ribosomes are translational machineries that catalyse protein synthesis. Ribosome structures from various species are known at the atomic level, but obtaining the structure of the human ribosome has remained a challenge; efforts to address this would be highly relevant with regard to human diseases. Here we report the near-atomic structure of the human ribosome derived from high-resolution single-particle cryo-electron microscopy and atomic model building. The structure has an average resolution of 3.6 Å, reaching 2.9 Å resolution in the most stable regions. It provides unprecedented insights into ribosomal RNA entities and amino acid side chains, notably of the transfer RNA binding sites and specific molecular interactions with the exit site tRNA. It reveals atomic details of the subunit interface, which is seen to remodel strongly upon rotational movements of the ribosomal subunits. Furthermore, the structure paves the way for analysing antibiotic side effects and diseases associated with deregulated protein synthesis.

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Figure 1: Overall structure of the human 80S ribosome.
Figure 2: Local resolution and electron density maps.
Figure 3: Conformational changes of the human ribosome.
Figure 4: Ribosomal inter-subunit bridges.
Figure 5: Molecular details of characteristic inter-subunit contacts.
Figure 6: Molecular recognition by the human ribosome at the level of the E-site tRNA.

Accession codes

Primary accessions

Electron Microscopy Data Bank

Protein Data Bank

Data deposits

The cryo-EM map and atomic coordinates have been deposited in the EMDB and Protein Data Bank under accession codes EMD-2938 and 4ug0, respectively.


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We thank A. Urzhumtsev and P. Afonine for discussions on FEM maps; R. Fritz and J. Michalon for IT support; R. Drui for constant high-quality engineers support; J.-F. Ménétret for technical support; H. Stark for discussions on Cs-correction; D. Moras and J.-C. Thierry for continuous encouragement in pushing structural biology frontiers; the IGBMC cell culture facilities for HeLa cell production; and the High Performance Computing Center of the University of Strasbourg funded by the Equipex Equip@Meso project. This long-term project (since 2003) was supported by the CNRS and the European Research Council (ERC Starting Grant N_243296 TRANSLATIONMACHINERY), and the electron microscope facility was supported by the Alsace Region, the FRM, the IBiSA platform program, INSERM, CNRS and the Association pour la Recherche sur le Cancer (ARC) and by the French Infrastructure for Integrated Structural Biology (FRISBI) ANR-10-INSB-05-01, and Instruct as part of the European Strategy Forum on Research Infrastructures (ESFRI).

Author information

H.K. conducted purification, optimization of samples for cryo-EM and cryo-EM data processing. A.G.M. performed cryo-EM data acquisition, image processing, structure refinement and model building. S.K.N. performed structure refinement and model building. B.P.K supervised the study. All authors analysed the data. B.P.K and H.K. wrote the manuscript, with input from A.G.M. and S.K.N.

Correspondence to Bruno P. Klaholz.

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The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 Resolution estimation.

The average resolution of the cryo-EM map as estimated from Fourier shell correlation according to the 0.143 criterion.

Extended Data Figure 2 Features of the refined cryo-EM 3D reconstruction.

Final cryo-EM map of the peptidyl-transferase centre region illustrating the high level of details observed.

Extended Data Figure 3 Typical electron density map regions of the human ribosome structure.

These final electron density maps were obtained by combining experimental amplitudes derived from the cryo-EM map and phases calculated from the iteratively refined atomic model, as done in standard refinement procedures in X-ray crystallography (see main text).

Extended Data Figure 4 Comparison of maps determined by cryo-EM and X-ray crystallography.

Top and middle, cryo-EM map and Phenix map of the human 80S ribosome (this study, A4546 region); bottom, crystal structure of a 70S ribosome at 2.8 Å resolution59 (corresponding A2600 region).

Extended Data Figure 5 Ribosomal protein structures.

a, b, Structure of ribosomal proteins uS2 and eS17.

Extended Data Figure 6 The decoding centre on the 40S.

a, Contact regions of the E-site tRNA on the 40S subunit. b, Catalytic PTC region of the ribosome, highlighting the partial structural disorder of a region of protein uL16 (loop), and disorder of residue U4548 (28S rRNA) in the absence of P-site tRNA, while all other residues are well-ordered. This suggests that the P-site pocket is largely pre-defined while U4548 and the loop participate in tRNA accommodation.

Extended Data Figure 7 Particle sorting scheme.

Particle sorting was done by 3D classification using six classes starting from 75,000 particles, resulting in two dominant classes with 10,000 and 45,000 particles, in rotated and non-rotated ribosome conformations respectively; the highest-resolution close-to-focus data set was refined using movie processing (see Methods).

Extended Data Table 1 Inter-subunit bridges and 60S and 40S residues involved in inter-subunit interactions

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Khatter, H., Myasnikov, A., Natchiar, S. et al. Structure of the human 80S ribosome. Nature 520, 640–645 (2015).

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