スーパーコンピューターによるシミュレーションが薬剤耐性菌の問題に挑む(Supercomputer simulation attacks problem of drug-resistant bacteria)

2023-09-20 ロスアラモス国立研究所(LANL)

<関連情報>

• https://discover.lanl.gov/news/0919-drug-resistance-bacteria/
• https://www.nature.com/articles/s41467-023-40404-9#Abs1

リボソームの触媒中心に対するアミノアシルtRNAの幾何学的アライメントがmRNAの正確な解読を支える Geometric alignment of aminoacyl-tRNA relative to catalytic centers of the ribosome underpins accurate mRNA decoding

Dylan Girodat,Hans-Joachim Wieden,Scott C. Blanchard & Karissa Y. Sanbonmatsu
Nature Communications  Published:11 September 2023
DOI:https://doi.org/10.1038/s41467-023-40404-9

Abstract

Accurate protein synthesis is determined by the two-subunit ribosome’s capacity to selectively incorporate cognate aminoacyl-tRNA for each mRNA codon. The molecular basis of tRNA selection accuracy, and how fidelity can be affected by antibiotics, remains incompletely understood. Using molecular simulations, we find that cognate and near-cognate tRNAs delivered to the ribosome by Elongation Factor Tu (EF-Tu) can follow divergent pathways of motion into the ribosome during both initial selection and proofreading. Consequently, cognate aa-tRNAs follow pathways aligned with the catalytic GTPase and peptidyltransferase centers of the large subunit, while near-cognate aa-tRNAs follow pathways that are misaligned. These findings suggest that differences in mRNA codon-tRNA anticodon interactions within the small subunit decoding center, where codon-anticodon interactions occur, are geometrically amplified over distance, as a result of this site’s physical separation from the large ribosomal subunit catalytic centers. These insights posit that the physical size of both tRNA and ribosome are key determinants of the tRNA selection fidelity mechanism.