8KAB

Mycobacterium smegmatis 50S ribosomal subunit-HflX complex

This is a non-PDB format compatible entry.

Summary for 8KAB

• Entry DOI: 10.2210/pdb8kab/pdb
• EMDB information: 37007
• Descriptor: 50S ribosomal protein bL37, 50S ribosomal protein L10, 50S ribosomal protein L11, ... (36 entities in total)
• Functional Keywords: complex, ribosome
• Biological source: Mycolicibacterium smegmatis MC2 155; More
• Total number of polymer chains: 35
• Total formula weight: 1538269.80

Authors

Srinivasan, K.,Banerjee, A.,Sengupta, J. (deposition date: 2023-08-02, release date: 2024-07-31, Last modification date: 2024-09-25)

Primary citation

Srinivasan, K.,Banerjee, A.,Sengupta, J.
Cryo-EM structures reveal the molecular mechanism of HflX-mediated erythromycin resistance in mycobacteria.
Structure, 32:1443-, 2024

PubMed Abstract: Mycobacterial HflX confers resistance against macrolide antibiotics. However, the exact molecular mechanism is poorly understood. To gain further insights, we determined the cryo-EM structures of M. smegmatis (Msm) HflX-50S subunit and 50S subunit-erythromycin (ERY) complexes at a global resolution of approximately 3 Å. A conserved nucleotide A2286 at the gate of nascent peptide exit tunnel (NPET) adopts a swayed conformation in HflX-50S complex and interacts with a loop within the linker helical (LH) domain of MsmHflX that contains an additional 9 residues insertion. Interestingly, the swaying of this nucleotide, which is usually found in the non-swayed conformation, is induced by erythromycin binding. Furthermore, we observed that erythromycin decreases HflX's ribosome-dependent GTP hydrolysis, resulting in its enhanced binding and anti-association activity on the 50S subunit. Our findings reveal how mycobacterial HflX senses the presence of macrolides at the peptide tunnel entrance and confers antibiotic resistance in mycobacteria.

PubMed: 39029461
DOI: 10.1016/j.str.2024.06.016

Experimental method

ELECTRON MICROSCOPY (3.3 Å)