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Yorodumi- EMDB-20216: Cryo-EM structure of an Acinetobacter baumannii multidrug efflux pump -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20216 | |||||||||
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Title | Cryo-EM structure of an Acinetobacter baumannii multidrug efflux pump | |||||||||
Map data | Acinetobacter baumannii multidrug efflux pump | |||||||||
Sample |
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Keywords | transporter / MEMBRANE PROTEIN | |||||||||
Function / homology | Hydrophobe/amphiphile efflux-1 HAE1 / Acriflavin resistance protein / Multidrug efflux transporter AcrB TolC docking domain, DN/DC subdomains / AcrB/AcrD/AcrF family / efflux transmembrane transporter activity / xenobiotic transmembrane transporter activity / plasma membrane / Efflux pump membrane transporter Function and homology information | |||||||||
Biological species | Acinetobacter baumannii (bacteria) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.98 Å | |||||||||
Authors | Su C-C | |||||||||
Funding support | United States, 1 items
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Citation | Journal: mBio / Year: 2019 Title: Cryo-Electron Microscopy Structure of an Acinetobacter baumannii Multidrug Efflux Pump. Authors: Chih-Chia Su / Christopher E Morgan / Sekhar Kambakam / Malligarjunan Rajavel / Harry Scott / Wei Huang / Corey C Emerson / Derek J Taylor / Phoebe L Stewart / Robert A Bonomo / Edward W Yu / Abstract: Resistance-nodulation-cell division multidrug efflux pumps are membrane proteins that catalyze the export of drugs and toxic compounds out of bacterial cells. Within the hydrophobe-amphiphile ...Resistance-nodulation-cell division multidrug efflux pumps are membrane proteins that catalyze the export of drugs and toxic compounds out of bacterial cells. Within the hydrophobe-amphiphile subfamily, these multidrug-resistant proteins form trimeric efflux pumps. The drug efflux process is energized by the influx of protons. Here, we use single-particle cryo-electron microscopy to elucidate the structure of the AdeB multidrug efflux pump embedded in lipidic nanodiscs to a resolution of 2.98 Å. We found that each AdeB molecule within the trimer preferentially takes the resting conformational state in the absence of substrates. We propose that proton influx and drug efflux are synchronized and coordinated within the transport cycle. is a successful human pathogen which has emerged as one of the most problematic and highly antibiotic-resistant Gram-negative bacteria worldwide. Multidrug efflux is a major mechanism that uses to counteract the action of multiple classes of antibiotics, such as β-lactams, tetracyclines, fluoroquinolones, and aminoglycosides. Here, we report a cryo-electron microscopy (cryo-EM) structure of the prevalent AdeB multidrug efflux pump, which indicates a plausible pathway for multidrug extrusion. Overall, our data suggest a mechanism for energy coupling that powers up this membrane protein to export antibiotics from bacterial cells. Our studies will ultimately inform an era in structure-guided drug design to combat multidrug resistance in these Gram-negative pathogens. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20216.map.gz | 326 MB | EMDB map data format | |
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Header (meta data) | emd-20216-v30.xml emd-20216.xml | 13.2 KB 13.2 KB | Display Display | EMDB header |
Images | emd_20216.png | 262.6 KB | ||
Filedesc metadata | emd-20216.cif.gz | 5.8 KB | ||
Others | emd_20216_additional.map.gz | 175 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20216 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20216 | HTTPS FTP |
-Validation report
Summary document | emd_20216_validation.pdf.gz | 537.3 KB | Display | EMDB validaton report |
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Full document | emd_20216_full_validation.pdf.gz | 536.9 KB | Display | |
Data in XML | emd_20216_validation.xml.gz | 7.9 KB | Display | |
Data in CIF | emd_20216_validation.cif.gz | 9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20216 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20216 | HTTPS FTP |
-Related structure data
Related structure data | 6owsMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_20216.map.gz / Format: CCP4 / Size: 347.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Acinetobacter baumannii multidrug efflux pump | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Acinetobacter baumannii multidrug efflux pump
File | emd_20216_additional.map | ||||||||||||
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Annotation | Acinetobacter baumannii multidrug efflux pump | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : AdeB
Entire | Name: AdeB |
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Components |
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-Supramolecule #1: AdeB
Supramolecule | Name: AdeB / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Acinetobacter baumannii (bacteria) |
-Supramolecule #2: RND transporter
Supramolecule | Name: RND transporter / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Acinetobacter baumannii (bacteria) |
-Macromolecule #1: Efflux pump membrane transporter
Macromolecule | Name: Efflux pump membrane transporter / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Acinetobacter baumannii (bacteria) |
Molecular weight | Theoretical: 112.588297 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MSQFFIRRPV FAWVIAIFII IFGLLSIPKL PIARFPSVAP PQVNISATYP GATAKTINDS VVTLIERELS GVKNLLYYSA TTDTSGTAE ITATFKPGTD VEMAQVDVQN KIKAVEARLP QVVRQQGLQV EASSSGFLML VGINSPNNQY SEVDLSDYLV R NVVEELKR ...String: MSQFFIRRPV FAWVIAIFII IFGLLSIPKL PIARFPSVAP PQVNISATYP GATAKTINDS VVTLIERELS GVKNLLYYSA TTDTSGTAE ITATFKPGTD VEMAQVDVQN KIKAVEARLP QVVRQQGLQV EASSSGFLML VGINSPNNQY SEVDLSDYLV R NVVEELKR VEGVGKVQSF GAEKAMRIWV DPNKLVSYGL SISDVNNAIR ENNVEIAPGR LGDLPAEKGQ LITIPLSAQG QL SSLEQFK NISLKSKTNG SVIKLSDVAN VEIGSQAYNF AILENGKPAT AAAIQLSPGA NAVKTAEGVR AKIEELKLNL PEG MEFSIP YDTAPFVKIS IEKVIHTLLE AMVLVFIVMY LFLHNVRYTL IPAIVAPIAL LGTFTVMLLA GFSINVLTMF GMVL AIGII VDDAIVVVEN VERIMATEGL SPKDATSKAM KEITSPIIGI TLVLAAVFLP MAFASGSVGV IYKQFTLTMS VSILF SALL ALILTPALCA TILKPIDGHH QKKGFFAWFD RSFDKVTKKY ELMLLKIIKH TVPMMVIFLV ITGITFAGMK YWPTAF MPE EDQGWFMTSF QLPSDATAER TRNVVNQFEN NLKDNPDVKS NTAILGWGFS GAGQNVAVAF TTLKDFKERT SSASKMT SD VNSSMANSTE GETMAVLPPA IDELGTFSGF SLRLQDRANL GMPALLAAQD ELMAMAAKNK KFYMVWNEGL PQGDNISL K IDREKLSALG VKFSDVSDII STSMGSMYIN DFPNQGRMQQ VIVQVEAKSR MQLKDILNLK VMGSSGQLVS LSEVVTPQW NKAPQQYNRY NGRPSLSIAG IPNFDTSSGE AMREMEQLIA KLPKGIGYEW TGISLQEKQS ESQMAFLLGL SMLVVFLVLA ALYESWAIP LSVMLVVPLG IFGAIIAIMS RGLMNDVFFK IGLITIIGLS AKNAILIVEF AKMLKEEGMS LIEATVAAAK L RLRPILMT SLAFTCGVIP LVIATGASSE TQHALGTGVF GGMISATILA IFFVPVFFIF ILGAVEKLFS SKKKISS UniProtKB: Efflux pump membrane transporter |
-Macromolecule #2: PHOSPHATIDYLETHANOLAMINE
Macromolecule | Name: PHOSPHATIDYLETHANOLAMINE / type: ligand / ID: 2 / Number of copies: 6 / Formula: PTY |
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Molecular weight | Theoretical: 734.039 Da |
Chemical component information | ChemComp-PTY: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | 2D array |
-Sample preparation
Concentration | 0.2 mg/mL |
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Buffer | pH: 7.5 |
Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 1.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.98 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 2) / Number images used: 142676 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: ANGULAR RECONSTITUTION |