8buu
From Proteopedia
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| == Structural highlights == | == Structural highlights == | ||
| <table><tr><td colspan='2'>[[8buu]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis_subsp._subtilis_str._168 Bacillus subtilis subsp. subtilis str. 168]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BUU FirstGlance]. <br> | <table><tr><td colspan='2'>[[8buu]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis_subsp._subtilis_str._168 Bacillus subtilis subsp. subtilis str. 168]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BUU FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=N:ANY+5-MONOPHOSPHATE+NUCLEOTIDE'>N</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.9Å</td></tr> | 
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=N:ANY+5-MONOPHOSPHATE+NUCLEOTIDE'>N</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8buu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8buu OCA], [https://pdbe.org/8buu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8buu RCSB], [https://www.ebi.ac.uk/pdbsum/8buu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8buu ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8buu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8buu OCA], [https://pdbe.org/8buu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8buu RCSB], [https://www.ebi.ac.uk/pdbsum/8buu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8buu ProSAT]</span></td></tr> | ||
| </table> | </table> | ||
| Line 13: | Line 14: | ||
| Genome-encoded antibiotic resistance (ARE) ATP-binding cassette (ABC) proteins of the F subfamily (ARE-ABCFs) mediate intrinsic resistance in diverse Gram-positive bacteria. The diversity of chromosomally-encoded ARE-ABCFs is far from being fully experimentally explored. Here we characterise phylogenetically diverse genome-encoded ABCFs from Actinomycetia (Ard1 from Streptomyces capreolus, producer of the nucleoside antibiotic A201A), Bacilli (VmlR2 from soil bacterium Neobacillus vireti) and Clostridia (CplR from Clostridium perfringens, Clostridium sporogenes and Clostridioides difficile). We demonstrate that Ard1 is a narrow spectrum ARE-ABCF that specifically mediates self-resistance against nucleoside antibiotics. The single-particle cryo-EM structure of a VmlR2-ribosome complex allows us to rationalise the resistance spectrum of this ARE-ABCF that is equipped with an unusually long antibiotic resistance determinant (ARD) subdomain. We show that CplR contributes to intrinsic pleuromutilin, lincosamide and streptogramin A resistance in Clostridioides, and demonstrate that C. difficile CplR (CDIF630_02847) synergises with the transposon-encoded 23S ribosomal RNA methyltransferase Erm to grant high levels of antibiotic resistance to the C. difficile 630 clinical isolate. Finally, assisted by uORF4u, our novel tool for detection of upstream open reading frames, we dissect the translational attenuation mechanism that controls the induction of cplR expression upon an antibiotic challenge. | Genome-encoded antibiotic resistance (ARE) ATP-binding cassette (ABC) proteins of the F subfamily (ARE-ABCFs) mediate intrinsic resistance in diverse Gram-positive bacteria. The diversity of chromosomally-encoded ARE-ABCFs is far from being fully experimentally explored. Here we characterise phylogenetically diverse genome-encoded ABCFs from Actinomycetia (Ard1 from Streptomyces capreolus, producer of the nucleoside antibiotic A201A), Bacilli (VmlR2 from soil bacterium Neobacillus vireti) and Clostridia (CplR from Clostridium perfringens, Clostridium sporogenes and Clostridioides difficile). We demonstrate that Ard1 is a narrow spectrum ARE-ABCF that specifically mediates self-resistance against nucleoside antibiotics. The single-particle cryo-EM structure of a VmlR2-ribosome complex allows us to rationalise the resistance spectrum of this ARE-ABCF that is equipped with an unusually long antibiotic resistance determinant (ARD) subdomain. We show that CplR contributes to intrinsic pleuromutilin, lincosamide and streptogramin A resistance in Clostridioides, and demonstrate that C. difficile CplR (CDIF630_02847) synergises with the transposon-encoded 23S ribosomal RNA methyltransferase Erm to grant high levels of antibiotic resistance to the C. difficile 630 clinical isolate. Finally, assisted by uORF4u, our novel tool for detection of upstream open reading frames, we dissect the translational attenuation mechanism that controls the induction of cplR expression upon an antibiotic challenge. | ||
| - | Genome-encoded ABCF factors implicated in intrinsic antibiotic resistance in Gram-positive bacteria: VmlR2, Ard1 and CplR.,Obana N, Takada H, Crowe-McAuliffe C, Iwamoto M, Egorov AA, Wu KJY, Chiba S, Murina V, Paternoga H, Tresco BIC, Nomura N, Myers AG, Atkinson GC, Wilson DN, Hauryliuk V Nucleic Acids Res. 2023  | + | Genome-encoded ABCF factors implicated in intrinsic antibiotic resistance in Gram-positive bacteria: VmlR2, Ard1 and CplR.,Obana N, Takada H, Crowe-McAuliffe C, Iwamoto M, Egorov AA, Wu KJY, Chiba S, Murina V, Paternoga H, Tresco BIC, Nomura N, Myers AG, Atkinson GC, Wilson DN, Hauryliuk V Nucleic Acids Res. 2023 May 22;51(9):4536-4554. doi: 10.1093/nar/gkad193. PMID:36951104<ref>PMID:36951104</ref> | 
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| </div> | </div> | ||
| <div class="pdbe-citations 8buu" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 8buu" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Ribosome 3D structures|Ribosome 3D structures]] | ||
| == References == | == References == | ||
| <references/> | <references/> | ||
Current revision
ARE-ABCF VmlR2 bound to a 70S ribosome
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