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Structural basis fo...
Structural basis for PoxtA-mediated resistance to phenicol and oxazolidinone antibiotics
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- Crowe-McAuliffe, Caillan (författare)
- Institute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, Hamburg, Germany
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- Murina, Victoriia (författare)
- Umeå universitet,Umeå University,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Turnbull, Kathryn Jane (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark,Copenhagen University Hospital
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- Huch, Susanne (författare)
- Karolinska Institutet,Karolinska Institute,SciLifeLab, Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet, Solna, Sweden
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- Kasari, Marje (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),University of Tartu, Institute of Technology, Tartu, Estonia
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- Takada, Hiraku (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo, Motoyama, Kita-ku, Kyoto, Japan
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- Nersisyan, Lilit (författare)
- Karolinska Institutet,Karolinska Institute,SciLifeLab, Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet, Solna, Sweden
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- Sundsfjord, Arnfinn (författare)
- Department of Microbiology and Infection Control, Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, University Hospital of North Norway, Tromsø, Norway; Research Group for Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
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- Hegstad, Kristin (författare)
- Department of Microbiology and Infection Control, Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, University Hospital of North Norway, Tromsø, Norway; Research Group for Host-Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
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- Atkinson, Gemma C (författare)
- Umeå universitet,Umeå University,Lund University,Lunds universitet,Proteinevolution,Forskargrupper vid Lunds universitet,Protein Evolution,Lund University Research Groups,Umeå Centre for Microbial Research (UCMR),Department of Experimental Medical Science, Lund University, Lund, Sweden
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- Pelechano, Vicent (författare)
- Karolinska Institutet,Karolinska Institute,SciLifeLab, Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet, Solna, Sweden
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- Wilson, Daniel N (författare)
- Institute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, Hamburg, Germany
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- Hauryliuk, Vasili (författare)
- Umeå universitet,Umeå University,Lund University,Lunds universitet,Molekylär enzymologi,Forskargrupper vid Lunds universitet,Molecular Enzymology,Lund University Research Groups,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten),University of Tartu, Institute of Technology, Tartu, Estonia; Department of Experimental Medical Science, Lund University, Lund, Sweden
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Polikanov, YS (författare)
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(creator_code:org_t)
- 2022-04-06
- 2022
- Engelska.
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- PoxtA and OptrA are ATP binding cassette (ABC) proteins of the F subtype (ABCF). They confer resistance to oxazolidinone and phenicol antibiotics, such as linezolid and chloramphenicol, which stall translating ribosomes when certain amino acids are present at a defined position in the nascent polypeptide chain. These proteins are often encoded on mobile genetic elements, facilitating their rapid spread amongst Gram-positive bacteria, and are thought to confer resistance by binding to the ribosome and dislodging the bound antibiotic. However, the mechanistic basis of this resistance remains unclear. Here we refine the PoxtA spectrum of action, demonstrate alleviation of linezolid-induced context-dependent translational stalling, and present cryo-electron microscopy structures of PoxtA in complex with the Enterococcus faecalis 70S ribosome. PoxtA perturbs the CCA-end of the P-site tRNA, causing it to shift by ∼4 Å out of the ribosome, corresponding to a register shift of approximately one amino acid for an attached nascent polypeptide chain. We postulate that the perturbation of the P-site tRNA by PoxtA thereby alters the conformation of the attached nascent chain to disrupt the drug binding site.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Anti-Bacterial Agents/pharmacology
- Cryoelectron Microscopy
- Drug Resistance, Bacterial/genetics
- Enterococcus faecalis/genetics
- Linezolid/pharmacology
- Oxazolidinones/pharmacology
- RNA, Transfer/genetics
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Crowe-McAuliffe, ...
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Murina, Victorii ...
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Turnbull, Kathry ...
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Huch, Susanne
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Kasari, Marje
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Takada, Hiraku
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visa fler...
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Nersisyan, Lilit
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Sundsfjord, Arnf ...
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Hegstad, Kristin
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Atkinson, Gemma ...
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Pelechano, Vicen ...
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Wilson, Daniel N
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Hauryliuk, Vasil ...
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Polikanov, YS
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- NATURVETENSKAP
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NATURVETENSKAP
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Lunds universitet
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Umeå universitet
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Karolinska Institutet