8G60

mRNA decoding in human is kinetically and structurally distinct from bacteria (CR state)

This is a non-PDB format compatible entry.

Summary for 8G60

• Entry DOI: 10.2210/pdb8g60/pdb
• EMDB information: 29757 29758 29759 29760 29766 29768 29771 29782
• Descriptor: 18S rRNA, uS5, eS6, ... (98 entities in total)
• Functional Keywords: human 80s, trna, mrna eef1a, eif5a, trna selection, ribosome
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 86
• Total formula weight: 4008673.72

Authors

Holm, M.,Natchiar, K.S.,Rundlet, E.J.,Myasnikov, A.G.,Altman, R.B.,Blanchard, S.C. (deposition date: 2023-02-14, release date: 2023-04-19, Last modification date: 2023-11-15)

Primary citation

Holm, M.,Natchiar, S.K.,Rundlet, E.J.,Myasnikov, A.G.,Watson, Z.L.,Altman, R.B.,Wang, H.Y.,Taunton, J.,Blanchard, S.C.
mRNA decoding in human is kinetically and structurally distinct from bacteria.
Nature, 617:200-207, 2023

PubMed Abstract: In all species, ribosomes synthesize proteins by faithfully decoding messenger RNA (mRNA) nucleotide sequences using aminoacyl-tRNA substrates. Current knowledge of the decoding mechanism derives principally from studies on bacterial systems. Although key features are conserved across evolution, eukaryotes achieve higher-fidelity mRNA decoding than bacteria. In human, changes in decoding fidelity are linked to ageing and disease and represent a potential point of therapeutic intervention in both viral and cancer treatment. Here we combine single-molecule imaging and cryogenic electron microscopy methods to examine the molecular basis of human ribosome fidelity to reveal that the decoding mechanism is both kinetically and structurally distinct from that of bacteria. Although decoding is globally analogous in both species, the reaction coordinate of aminoacyl-tRNA movement is altered on the human ribosome and the process is an order of magnitude slower. These distinctions arise from eukaryote-specific structural elements in the human ribosome and in the elongation factor eukaryotic elongation factor 1A (eEF1A) that together coordinate faithful tRNA incorporation at each mRNA codon. The distinct nature and timing of conformational changes within the ribosome and eEF1A rationalize how increased decoding fidelity is achieved and potentially regulated in eukaryotic species.

PubMed: 37020024
DOI: 10.1038/s41586-023-05908-w

Experimental method

ELECTRON MICROSCOPY (2.54 Å)