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Structural basis fo...
Structural basis for HflXr-mediated antibiotic resistance in Listeria monocytogenes
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- Koller, Timm O (author)
- Institute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, Hamburg, Germany
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- Turnbull, Kathryn Jane (author)
- Umeå universitet,Umeå University,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark
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- Vaitkevicius, Karolis (author)
- Umeå universitet,Umeå University,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Crowe-McAuliffe, Caillan (author)
- Institute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, Hamburg, Germany
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- Roghanian, Mohammad (author)
- Umeå universitet,Umeå University,Lund University,Lunds universitet,Molekylär enzymologi,Forskargrupper vid Lunds universitet,Molecular Enzymology,Lund University Research Groups,Copenhagen University Hospital,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark; Department of Experimental Medical Science, Lund University, Lund, Sweden
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- Bulvas, Ondřej (author)
- Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nam. 2, Prague 6, Czech Republic; Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technicka 5, Prague 6, Czech Republic
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- Nakamoto, Jose A (author)
- Lund University,Lunds universitet,Proteinevolution,Forskargrupper vid Lunds universitet,Protein Evolution,Lund University Research Groups,Department of Experimental Medical Science, Lund University, Lund, Sweden
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- Kurata, Tatsuaki (author)
- 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),Department of Experimental Medical Science, Lund University, Lund, Sweden
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- Julius, Christina (author)
- Umeå universitet,Umeå University,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Atkinson, Gemma C (author)
- Lund University,Lunds universitet,Proteinevolution,Forskargrupper vid Lunds universitet,Protein Evolution,Lund University Research Groups,Department of Experimental Medical Science, Lund University, Lund, Sweden
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- Johansson, Jörgen (author)
- Umeå universitet,Umeå University,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
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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,Department of Experimental Medical Science, Lund University, Lund, Sweden; University of Tartu, Institute of Technology, Tartu, Estonia,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Wilson, Daniel N (author)
- Institute for Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, Hamburg, Germany
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(creator_code:org_t)
- 2022-10-27
- 2022
- English.
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 50:19, s. 11285-11300
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- cryo-electron microscopy (cryo-EM)
- antibiotic resisitance
- ribosome
Publication and Content Type
- art (subject category)
- ref (subject category)
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Koller, Timm O
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Turnbull, Kathry ...
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Vaitkevicius, Ka ...
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Crowe-McAuliffe, ...
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Roghanian, Moham ...
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Bulvas, Ondřej
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Nakamoto, Jose A
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Kurata, Tatsuaki
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Julius, Christin ...
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Atkinson, Gemma ...
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Johansson, Jörge ...
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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 Microbiology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Structural Biolo ...
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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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Nucleic Acids Re ...
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Lund University
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Umeå University