EMD-38631

Single-particle
3.2 Å
EMD-38631 Deposition: 10/01/2024
Map released: 10/07/2024
Last modified: 10/07/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-38631

Cryo-EM structure of the human 80S ribosome with Tigecycline, E-tRNA and P-tRNA

EMD-38631

Single-particle
3.2 Å
EMD-38631 Deposition: 10/01/2024
Map released: 10/07/2024
Last modified: 10/07/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: 80S ribosome with tigecycline, E-tRNA and P-tRNA
Fitted models: 8xsz

Deposition Authors: Li X, Wang M, Cheng J
Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline.
Li X, Wang M, Denk T , Buschauer R, Li Y, Beckmann R , Cheng J
(2024) Nat Commun , 15 , 5481 - 5481
PUBMED: 38942792
DOI: doi:10.1038/s41467-024-49797-7
ISSN: 2041-1723
Abstract:
Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy.