8vr4

Structure of Mycobacterium smegmatis 50S ribosomal subunit bound to HflX and erythromycin:50S-HflX-A-Ery

spinqualitylabelsall models 8vr4, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8vr4 is a 10 chain structure with sequence from Mycolicibacterium smegmatis MC2 155. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.8Å Ligands: ERY, GCP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL30_MYCS2 Publication Abstract from PubMed 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. HflX-mediated drug resistance through ribosome splitting and rRNA disordering in mycobacteria.,Majumdar S, Kashyap A, Koripella RK, Sharma MR, Hurst-Hess K, Manjari SR, Banavali NK, Ghosh P, Agrawal RK Proc Natl Acad Sci U S A. 2025 Feb 11;122(6):e2419826122. doi: , 10.1073/pnas.2419826122. Epub 2025 Feb 6. PMID:39913204 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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