Rumicidins are a family of mammalian host-defense peptides plugging the 70S ribosome exit tunnel

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.

Авторы: Panteleev Pavel V., Pichkur Eugene B., Kruglikov Roman N., Paleskava Alena, Shulenina Olga V., Bolosov Ilia A., Bogdanov Ivan V., Safronova Victoria N., Balandin Sergey V., Marina Valeriya I., Kombarova Tatiana I., Korobova Olga V., Shamova Olga V., Myasnikov Alexander G., Borzilov Alexander I., Osterman Ilya A., Sergiev Petr V., Bogdanov Alexey A., Dontsova Olga A., Konevega Andrey L., Ovchinnikova Tatiana V.
Журнал: Nature communications
Том: 15
Номер: 1
Год издания: 2024
Издательство: Nature Pub. Group
Местоположение издательства: United Kingdom
Номер статьи: 8925
DOI: 10.1038/s41467-024-53309-y
Аннотация: 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 theEscherichia coli 70S ribosome in complex with one of the representatives of the family revealed that the binding site of rumicidins span the ribosomalA-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 theMacAB-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 fordevelopment of ribosome-targeting antibiotics.
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Rumicidins are a family of mammalian host-defense peptides plugging the 70S ribosome exit tunnelстатья

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