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4u8y

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Revision as of 08:49, 4 August 2016

Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB

Structural highlights

4u8y is a 5 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4u8v
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ACRB_ECOLI] AcrAB is a drug efflux protein with a broad substrate specificity.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Membrane transporters of the RND superfamily confer multidrug resistance to pathogenic bacteria, and are essential for cholesterol metabolism and embryonic development in humans. We use high-resolution X-ray crystallography and computational methods to delineate the mechanism of the homotrimeric RND-type proton/drug antiporter AcrB, the active component of the major efflux system AcrAB-TolC in Escherichia coli, and one most complex and intriguing membrane transporters known to date. Analysis of wildtype AcrB and four functionally-inactive variants reveals an unprecedented mechanism that involves two remote alternating-access conformational cycles within each protomer, namely one for protons in the transmembrane region and another for drugs in the periplasmic domain, 50 A apart. Each of these cycles entails two distinct types of collective motions of two structural repeats, coupled by flanking alpha-helices that project from the membrane. Moreover, we rationalize how the cross-talk among protomers across the trimerization interface might lead to a more kinetically efficient efflux system.

Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB.,Eicher T, Seeger MA, Anselmi C, Zhou W, Brandstatter L, Verrey F, Diederichs K, Faraldo-Gomez JD, Pos KM Elife. 2014 Sep 19;3. doi: 10.7554/eLife.03145. PMID:25248080^[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
↑ Eicher T, Seeger MA, Anselmi C, Zhou W, Brandstatter L, Verrey F, Diederichs K, Faraldo-Gomez JD, Pos KM. Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB. Elife. 2014 Sep 19;3. doi: 10.7554/eLife.03145. PMID:25248080 doi:http://dx.doi.org/10.7554/eLife.03145

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4u8y"

Categories: Pos, K M | Darpin | Membrane protein | Multidrug efflux protein | Transport protein

@@ Line 1: / Line 1: @@
 ==Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB==
 <StructureSection load='4u8y' size='340' side='right' caption='[[4u8y]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=MIY:(4S,4AS,5AR,12AS)-4,7-BIS(DIMETHYLAMINO)-3,10,12,12A-TETRAHYDROXY-1,11-DIOXO-1,4,4A,5,5A,6,11,12A-OCTAHYDROTETRACENE-2-CARBOXAMIDE'>MIY</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u8v|4u8v]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u8y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u8y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u8y RCSB], [http://www.ebi.ac.uk/pdbsum/4u8y PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u8y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u8y OCA], [http://pdbe.org/4u8y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u8y RCSB], [http://www.ebi.ac.uk/pdbsum/4u8y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u8y ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4u8y" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4u8y

From Proteopedia

Revision as of 08:49, 4 August 2016

Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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