| Structural highlights
Function
[ACRB_ECOLI] AcrAB is a drug efflux protein with a broad substrate specificity.[1] [2] [3]
Publication Abstract from PubMed
Membrane proteins function in native cell membranes, but extraction into isolated particles is needed for many biochemical and structural analyses. Commonly used detergent-extraction methods destroy naturally associated lipid bilayers. Here, we devised a detergent-free method for preparing cell-membrane nanoparticles to study the multidrug exporter AcrB, by cryo-EM at 3.2-A resolution. We discovered a remarkably well-organized lipid-bilayer structure associated with transmembrane domains of the AcrB trimer. This bilayer patch comprises 24 lipid molecules; inner leaflet chains are packed in a hexagonal array, whereas the outer leaflet has highly irregular but ordered packing. Protein side chains interact with both leaflets and participate in the hexagonal pattern. We suggest that the lipid bilayer supports and harmonizes peristaltic motions through AcrB trimers. In AcrB D407A, a putative proton-relay mutant, lipid bilayer buttresses protein interactions lost in crystal structures after detergent-solubilization. Our detergent-free system preserves lipid-protein interactions for visualization and should be broadly applicable.
Structure and activity of lipid bilayer within a membrane-protein transporter.,Qiu W, Fu Z, Xu GG, Grassucci RA, Zhang Y, Frank J, Hendrickson WA, Guo Y Proc Natl Acad Sci U S A. 2018 Dec 3. pii: 1812526115. doi:, 10.1073/pnas.1812526115. PMID:30509977[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
- ↑ Qiu W, Fu Z, Xu GG, Grassucci RA, Zhang Y, Frank J, Hendrickson WA, Guo Y. Structure and activity of lipid bilayer within a membrane-protein transporter. Proc Natl Acad Sci U S A. 2018 Dec 3. pii: 1812526115. doi:, 10.1073/pnas.1812526115. PMID:30509977 doi:http://dx.doi.org/10.1073/pnas.1812526115
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