8VIO

Structure of Mycobacterium smegmatis HflX bound to a 70S ribosome

これはPDB形式変換不可エントリーです。

8VIO の概要

• エントリーDOI: 10.2210/pdb8vio/pdb
• EMDBエントリー: 43267
• 分子名称: 50S Ribosomal Protein L28, 30S ribosomal protein S11, 30S ribosomal protein S12, ... (57 entities in total)
• 機能のキーワード: ribosome splitting, mycobacterium smegmatis 70s, hflx, translation, ribosome
• 由来する生物種: Mycolicibacterium smegmatis MC2 155; 詳細
• タンパク質・核酸の鎖数: 57
• 化学式量合計: 2355618.65

構造登録者

Majumdar, S.,Koripella, R.K.,Sharma, M.R.,Manjari, S.R.,Banavali, N.K.,Agrawal, R.K. (登録日: 2024-01-05, 公開日: 2025-02-19, 最終更新日: 2025-04-30)

主引用文献

Majumdar, S.,Kashyap, A.,Koripella, R.K.,Sharma, M.R.,Hurst-Hess, K.,Manjari, S.R.,Banavali, N.K.,Ghosh, P.,Agrawal, R.K.
HflX-mediated drug resistance through ribosome splitting and rRNA disordering in mycobacteria.
Proc.Natl.Acad.Sci.USA, 122:e2419826122-e2419826122, 2025

PubMed Abstract: HflX is a highly conserved ribosome-associated GTPase implicated in rescuing stalled ribosomes and mediating antibiotic resistance in several bacteria, including macrolide-lincosamide antibiotic resistance in mycobacteria. Mycobacterial HflXs carry a distinct N-terminal extension (NTE) and a small insertion, as compared to their eubacterial homologs. Here, we present several high-resolution cryo-EM structures of mycobacterial HflX in complex with the 70S ribosome and its 50S subunit, with and without antibiotics. These structures reveal a distinct mechanism for HflX-mediated ribosome splitting and antibiotic resistance in mycobacteria. Our findings indicate that the NTE of mycobacterial HflX induces persistent disordering of multiple 23S rRNA helices, facilitating the dissociation of the 70S ribosome and generating an inactive pool of 50S subunits. During this process, HflX undergoes a large conformational change that stabilizes its NTE. Mycobacterial HflX also acts as an anti-association factor by binding to predissociated 50S subunits. Our structures show that a mycobacteria-specific insertion in HflX reaches far into the peptidyl transferase center (PTC), such that it would overlap with the ribosome-bound macrolide antibiotics. However, in the presence of antibiotics, this insertion retracts, adjusts around, and interacts with the antibiotic molecules. These results suggest that mycobacterial HflX is agnostic to antibiotic presence in the PTC. It mediates antibiotic resistance by splitting antibiotic-stalled 70S ribosomes and inactivating the resulting 50S subunits.

PubMed: 39913204
DOI: 10.1073/pnas.2419826122

実験手法

ELECTRON MICROSCOPY (3.26 Å)