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Structural basis of...
Structural basis of ABCF-mediated resistance to pleuromutilin, lincosamide, and streptogramin A antibiotics in Gram-positive pathogens
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- Crowe-McAuliffe, Caillan (author)
- Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany
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- Murina, Victoriia (author)
- Umeå universitet,Umeå University,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Turnbull, Kathryn Jane (author)
- Umeå universitet,Umeå University,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Kasari, Marje (author)
- University of Tartu, Institute of Technology, Tartu, Estonia
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- Mohamad, Merianne (author)
- Astbury Centre for Structural Molecular Biology, School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
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- Polte, Christine (author)
- Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany
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- Takada, Hiraku (author)
- Umeå universitet,Umeå University,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Vaitkevicius, Karolis (author)
- Umeå universitet,Umeå University,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Johansson, Jörgen (author)
- Umeå universitet,Umeå University,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Astbury Centre for Structural Molecular Biology, School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
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- Ignatova, Zoya (author)
- Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany
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- Atkinson, Gemma C. (author)
- Umeå universitet,Umeå University,Institutionen för molekylärbiologi (Medicinska fakulteten),Molekylär Infektionsmedicin, Sverige (MIMS)
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- O’Neill, Alex J. (author)
- University of Leeds
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- Hauryliuk, Vasili (author)
- Umeå universitet,Umeå University,Lund University,Lunds universitet,Molekylär enzymologi,Forskargrupper vid Lunds universitet,Molecular Enzymology,Lund University Research Groups,University of Tartu, Institute of Technology, Tartu, Estonia; Department of Experimental Medical Science, Lund University, Lund, Sweden,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Wilson, Daniel N. (author)
- Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany
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(creator_code:org_t)
- 2021-06-11
- 2021
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Abstract
Subject headings
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- Target protection proteins confer resistance to the host organism by directly binding to the antibiotic target. One class of such proteins are the antibiotic resistance (ARE) ATP-binding cassette (ABC) proteins of the F-subtype (ARE-ABCFs), which are widely distributed throughout Gram-positive bacteria and bind the ribosome to alleviate translational inhibition from antibiotics that target the large ribosomal subunit. Here, we present single-particle cryo-EM structures of ARE-ABCF-ribosome complexes from three Gram-positive pathogens: Enterococcus faecalis LsaA, Staphylococcus haemolyticus VgaALC and Listeria monocytogenes VgaL. Supported by extensive mutagenesis analysis, these structures enable a general model for antibiotic resistance mediated by these ARE-ABCFs to be proposed. In this model, ABCF binding to the antibiotic-stalled ribosome mediates antibiotic release via mechanistically diverse long-range conformational relays that converge on a few conserved ribosomal RNA nucleotides located at the peptidyltransferase center. These insights are important for the future development of antibiotics that overcome such target protection resistance mechanisms.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
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- By the author/editor
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Crowe-McAuliffe, ...
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Murina, Victorii ...
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Turnbull, Kathry ...
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Kasari, Marje
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Mohamad, Meriann ...
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Polte, Christine
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show more...
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Takada, Hiraku
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Vaitkevicius, Ka ...
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Johansson, Jörge ...
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Ignatova, Zoya
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Atkinson, Gemma ...
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O’Neill, Alex J.
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Hauryliuk, Vasil ...
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Wilson, Daniel N ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
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Nature Communica ...
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Lund University
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Umeå University