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| | <StructureSection load='6sgs' size='340' side='right'caption='[[6sgs]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='6sgs' size='340' side='right'caption='[[6sgs]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6sgs]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli], [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences] and [http://en.wikipedia.org/wiki/Shigella_boydii_965-58 Shigella boydii 965-58]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SGS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SGS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6sgs]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12], [https://en.wikipedia.org/wiki/Shigella_boydii_965-58 Shigella boydii 965-58] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SGS FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">acrB, acrE, b0462, JW0451 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI]), acrZ, SB96558_0924 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=766138 Shigella boydii 965-58])</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]] 3.2Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6sgs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sgs OCA], [http://pdbe.org/6sgs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sgs RCSB], [http://www.ebi.ac.uk/pdbsum/6sgs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sgs 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=6sgs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sgs OCA], [https://pdbe.org/6sgs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sgs RCSB], [https://www.ebi.ac.uk/pdbsum/6sgs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sgs ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACRB_ECOLI ACRB_ECOLI]] AcrAB is a drug efflux protein with a broad substrate specificity.<ref>PMID:16915237</ref> <ref>PMID:16946072</ref> <ref>PMID:17194213</ref> [[http://www.uniprot.org/uniprot/I6DQK7_SHIBO I6DQK7_SHIBO]] AcrA-AcrB-AcrZ-TolC is a drug efflux protein complex with a broad substrate specificity. This protein binds to AcrB and is required for efflux of some but not all substrates, suggesting it may influence the specificity of drug export.[HAMAP-Rule:MF_01484] | + | [https://www.uniprot.org/uniprot/ACRB_ECOLI ACRB_ECOLI] AcrAB is a drug efflux protein with a broad substrate specificity.<ref>PMID:16915237</ref> <ref>PMID:16946072</ref> <ref>PMID:17194213</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Shigella boydii 965-58]] | | [[Category: Shigella boydii 965-58]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Du, D]] | + | [[Category: Du D]] |
| - | [[Category: Luisi, B F]] | + | [[Category: Luisi BF]] |
| - | [[Category: Neuberger, A]] | + | [[Category: Neuberger A]] |
| - | [[Category: Newman, C]] | + | [[Category: Newman C]] |
| - | [[Category: Szewczak-Harris, A]] | + | [[Category: Szewczak-Harris A]] |
| - | [[Category: Antibiotic resistance]]
| + | |
| - | [[Category: Drug transport]]
| + | |
| - | [[Category: Efflux pump]]
| + | |
| - | [[Category: Lipid nanodisc]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Rnd transporter]]
| + | |
| Structural highlights
Function
ACRB_ECOLI AcrAB is a drug efflux protein with a broad substrate specificity.[1] [2] [3]
Publication Abstract from PubMed
The small protein AcrZ in Escherichia coli interacts with the transmembrane portion of the multidrug efflux pump AcrB and increases resistance of the bacterium to a subset of the antibiotic substrates of that transporter. It is not clear how the physical association of the two proteins selectively changes activity of the pump for defined substrates. Here, we report cryo-EM structures of AcrB and the AcrBZ complex in lipid environments, and comparisons suggest that conformational changes occur in the drug-binding pocket as a result of AcrZ binding. Simulations indicate that cardiolipin preferentially interacts with the AcrBZ complex, due to increased contact surface, and we observe that chloramphenicol sensitivity of bacteria lacking AcrZ is exacerbated when combined with cardiolipin deficiency. Taken together, the data suggest that AcrZ and lipid cooperate to allosterically modulate AcrB activity. This mode of regulation by a small protein and lipid may occur for other membrane proteins.
Interactions of a Bacterial RND Transporter with a Transmembrane Small Protein in a Lipid Environment.,Du D, Neuberger A, Orr MW, Newman CE, Hsu PC, Samsudin F, Szewczak-Harris A, Ramos LM, Debela M, Khalid S, Storz G, Luisi BF Structure. 2020 Apr 16. pii: S0969-2126(20)30095-2. doi:, 10.1016/j.str.2020.03.013. PMID:32348749[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A. Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature. 2006 Sep 14;443(7108):173-9. Epub 2006 Aug 16. PMID:16915237 doi:10.1038/nature05076
- ↑ Seeger MA, Schiefner A, Eicher T, Verrey F, Diederichs K, Pos KM. Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science. 2006 Sep 1;313(5791):1295-8. PMID:16946072 doi:313/5791/1295
- ↑ Sennhauser G, Amstutz P, Briand C, Storchenegger O, Grutter MG. Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors. PLoS Biol. 2007 Jan;5(1):e7. PMID:17194213 doi:10.1371/journal.pbio.0050007
- ↑ Du D, Neuberger A, Orr MW, Newman CE, Hsu PC, Samsudin F, Szewczak-Harris A, Ramos LM, Debela M, Khalid S, Storz G, Luisi BF. Interactions of a Bacterial RND Transporter with a Transmembrane Small Protein in a Lipid Environment. Structure. 2020 Apr 16. pii: S0969-2126(20)30095-2. doi:, 10.1016/j.str.2020.03.013. PMID:32348749 doi:http://dx.doi.org/10.1016/j.str.2020.03.013
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