8kab
Mycobacterium smegmatis 50S ribosomal subunit-HflX complexMycobacterium smegmatis 50S ribosomal subunit-HflX complex
Structural highlights
FunctionRL23_MYCS2 One of the early assembly proteins it binds 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the ribosome. Forms the main docking site for trigger factor binding to the ribosome.[HAMAP-Rule:MF_01369] Publication Abstract from PubMedMycobacterial 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 A. 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. Cryo-EM structures reveal the molecular mechanism of HflX-mediated erythromycin resistance in mycobacteria.,Srinivasan K, Banerjee A, Sengupta J Structure. 2024 Jul 8:S0969-2126(24)00234-X. doi: 10.1016/j.str.2024.06.016. PMID:39029461[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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