9D89

E. coli 50S ribosomal subunit in complex with PrAMP rumicidin-2 (focused refinement)

Summary for 9D89

• Entry DOI: 10.2210/pdb9d89/pdb
• EMDB information: 46632
• Descriptor: 50S ribosomal protein L33, 50S ribosomal protein L15, 50S ribosomal protein L17, ... (36 entities in total)
• Functional Keywords: proline-rich antimicrobial peptides, pramp, ribosome, cryo-em
• Biological source: Escherichia coli; More
• Total number of polymer chains: 31
• Total formula weight: 1280904.67

Authors

Pichkur, E.B.,Panteleev, P.V.,Konevega, A.L. (deposition date: 2024-08-19, release date: 2025-01-22, Last modification date: 2025-03-19)

Primary citation

Panteleev, P.V.,Pichkur, E.B.,Kruglikov, R.N.,Paleskava, A.,Shulenina, O.V.,Bolosov, I.A.,Bogdanov, I.V.,Safronova, V.N.,Balandin, S.V.,Marina, V.I.,Kombarova, T.I.,Korobova, O.V.,Shamova, O.V.,Myasnikov, A.G.,Borzilov, A.I.,Osterman, I.A.,Sergiev, P.V.,Bogdanov, A.A.,Dontsova, O.A.,Konevega, A.L.,Ovchinnikova, T.V.
Rumicidins are a family of mammalian host-defense peptides plugging the 70S ribosome exit tunnel.
Nat Commun, 15:8925-8925, 2024

PubMed Abstract: The antimicrobial resistance crisis along with challenges of antimicrobial discovery revealed the vital necessity to develop new antibiotics. Many of the animal proline-rich antimicrobial peptides (PrAMPs) inhibit the process of bacterial translation. Genome projects allowed to identify immune-related genes encoding animal host defense peptides. Here, using genome mining approach, we discovered a family of proline-rich cathelicidins, named rumicidins. The genes encoding these peptides are widespread among ruminant mammals. Biochemical studies indicated that rumicidins effectively inhibited the elongation stage of bacterial translation. The cryo-EM structure of the Escherichia coli 70S ribosome in complex with one of the representatives of the family revealed that the binding site of rumicidins span the ribosomal A-site cleft and the nascent peptide exit tunnel interacting with its constriction point by the conservative Trp23-Phe24 dyad. Bacterial resistance to rumicidins is mediated by knockout of the SbmA transporter or modification of the MacAB-TolC efflux pump. A wide spectrum of antibacterial activity, a high efficacy in the animal infection model, and lack of adverse effects towards human cells in vitro make rumicidins promising molecular scaffolds for development of ribosome-targeting antibiotics.

PubMed: 39414793
DOI: 10.1038/s41467-024-53309-y

Experimental method

ELECTRON MICROSCOPY (1.95 Å)