7P2E

Human mitochondrial ribosome small subunit in complex with IF3, GMPPMP and streptomycin

これはPDB形式変換不可エントリーです。

7P2E の概要

• エントリーDOI: 10.2210/pdb7p2e/pdb
• EMDBエントリー: 13170
• 分子名称: 12S mitochondrial rRNA, 28S ribosomal protein S12, mitochondrial, 28S ribosomal protein S14, mitochondrial, ... (42 entities in total)
• 機能のキーワード: initiation factor 3, translation, antibiotic, streptomycin, ribosome
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 32
• 化学式量合計: 1179810.98

構造登録者

Itoh, Y.,Khawaja, A.,Singh, V.,Rorbach, J.,Amunts, A. (登録日: 2021-07-05, 公開日: 2022-07-27, 最終更新日: 2024-04-24)

主引用文献

Itoh, Y.,Singh, V.,Khawaja, A.,Naschberger, A.,Nguyen, M.D.,Rorbach, J.,Amunts, A.
Structure of the mitoribosomal small subunit with streptomycin reveals Fe-S clusters and physiological molecules.
Elife, 11:-, 2022

PubMed Abstract: The mitoribosome regulates cellular energy production, and its dysfunction is associated with aging. Inhibition of the mitoribosome can be caused by off-target binding of antimicrobial drugs and was shown to be coupled with a bilateral decreased visual acuity. Previously, we reported mitochondria-specific protein aspects of the mitoribosome, and in this article we present a 2.4-Å resolution structure of the small subunit in a complex with the anti-tuberculosis drug streptomycin that reveals roles of non-protein components. We found iron-sulfur clusters that are coordinated by different mitoribosomal proteins, nicotinamide adenine dinucleotide (NAD) associated with rRNA insertion, and posttranslational modifications. This is the first evidence of inter-protein coordination of iron-sulfur, and the finding of iron-sulfur clusters and NAD as fundamental building blocks of the mitoribosome directly links to mitochondrial disease and aging. We also report details of streptomycin interactions, suggesting that the mitoribosome-bound streptomycin is likely to be in hydrated gem-diol form and can be subjected to other modifications by the cellular milieu. The presented approach of adding antibiotics to cultured cells can be used to define their native structures in a bound form under more physiological conditions, and since streptomycin is a widely used drug for treatment, the newly resolved features can serve as determinants for targeting.

PubMed: 36480258
DOI: 10.7554/eLife.77460

実験手法

ELECTRON MICROSCOPY (2.4 Å)