期刊
NUCLEIC ACIDS RESEARCH
卷 50, 期 19, 页码 11285-11300出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkac934
关键词
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资金
- Deutsche Forschungsgemeinschaft (DFG) [WI3285/8-1]
- Swedish Research Council (Vetenskapsradet) [2017-03783, 2021-01146, 2019-01085, 2020-020053]
- Stiftelsen Olle Engkvist Byggm astare
- Ragnar Soderbergs Stiftelse
- European Union [2014-2020.4.01.15-0013]
- Estonian Research Council [PRG335]
- Interreg OKS [NYPS 20201844]
- Crafoord foundation [20220562]
- Deutsche Zentrum fuur Luft-und Raumfahrt [DLR01Kl1820]
- Swedish Research Council [2018-00956]
- Knut and Alice Wallenberg Foundation [2020-0037]
- Knut and Alice Wallenberg
- Family Erling Persson Foundation
- Kempe Foundation
- SciLifeLab, Stockholm University
- Umea University
- University of Hamburg
- Swedish Research Council [2021-01146, 2018-00956, 2017-03783, 2019-01085] Funding Source: Swedish Research Council
- Vinnova [2019-01085] Funding Source: Vinnova
HflX and HflXr are bacterial GTPases, but HflXr confers resistance to certain antibiotics through an allosteric ribosome protection mechanism.
HflX is a ubiquitous bacterial GTPase that splits and recycles stressed ribosomes. In addition to HflX, Listeria monocytogenes contains a second HflX homolog, HflXr. Unlike HflX, HflXr confers resistance to macrolide and lincosamide antibiotics by an experimentally unexplored mechanism. Here, we have determined cryo-EM structures of L. monocytogenes HflXr-50S and HflX-50S complexes as well as L. monocytogenes 70S ribosomes in the presence and absence of the lincosamide lincomycin. While the overall geometry of HflXr on the 50S subunit is similar to that of HflX, a loop within the N-terminal domain of HflXr, which is two amino acids longer than in HflX, reaches deeper into the peptidyltransferase center. Moreover, unlike HflX, the binding of HflXr induces conformational changes within adjacent rRNA nucleotides that would be incompatible with drug binding. These findings suggest that HflXr confers resistance using an allosteric ribosome protection mechanism, rather than by simply splitting and recycling antibiotic-stalled ribosomes.
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