ArticleThe Journal of biological chemistry2010
Lipid composition regulates the orientation of transmembrane helices in HorA, an ABC multidrug transporter.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 43 citations in OpenAlex.
- Metabolome and Transcriptome Combinatory Profiling Reveals Fluconazole Resistance Mechanisms ofMicroorganisms · 2023Article
- A comparative study of interfacial environments in lipid nanodiscs and vesicles.Biophysical reports · 2022Article
- Recombinant and endogenous ways to produce methylated phospholipids in Escherichia coli.Applied microbiology and biotechnology · 2021Article
- Selective Nutrient Transport in Bacteria: Multicomponent Transporter Systems Reign Supreme.Frontiers in molecular biosciences · 2021Review
- How bilayer properties influence membrane protein folding.Protein science : a publication of the Protein Society · 2020Review
- Emerging Diversity in Lipid-Protein Interactions.Chemical reviews · 2019Review
- Lipid-Dependent Alternating Access Mechanism of a Bacterial Multidrug ABC Exporter.ACS central science · 2019Article
- Transport rates of a glutamate transporter homologue are influenced by the lipid bilayer.The Journal of biological chemistry · 2015Article
- Legionella dumoffii utilizes exogenous choline for phosphatidylcholine synthesis.International journal of molecular sciences · 2014Article
- Membrane lipids in Agrobacterium tumefaciens: biosynthetic pathways and importance for pathogenesis.Frontiers in plant science · 2014Review
- Structural evidence for functional lipid interactions in the betaine transporter BetP.The EMBO journal · 2013Article
- Proper fatty acid composition rather than an ionizable lipid amine is required for full transport function of lactose permease from Escherichia coli.The Journal of biological chemistry · 2013Article
- The lipid network.Biophysical reviews · 2012Review
- Molecular cloning and functional characterization of an ATP-binding cassette transporter OtrC from Streptomyces rimosus.BMC biotechnology · 2012Article
- Time-resolved Fourier transform infrared spectroscopy of the nucleotide-binding domain from the ATP-binding Cassette transporter MsbA: ATP hydrolysis is the rate-limiting step in the catalytic cycle.The Journal of biological chemistry · 2012Article
- Molecular genetic and biochemical approaches for defining lipid-dependent membrane protein folding.Biochimica et biophysica acta · 2012Review
- Optimized purification of a heterodimeric ABC transporter in a highly stable form amenable to 2-D crystallization.PloS one · 2011Article
- Plasticity of lipid-protein interactions in the function and topogenesis of the membrane protein lactose permease from Escherichia coli.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
ATP-binding cassette (ABC) transporters constitute a large class of molecular pumps whose central role in chemotherapy resistance has highlighted their clinical relevance. We investigated whether the lipid composition of the membrane affects the function and structure of HorA, a bacterial ABC multidrug transporter. When the transporter was reconstituted in a bilayer where phosphatidylethanolamine (PE), the main lipid of the bacterial membrane, was replaced with phosphatidylcholine (PC), ATP hydrolysis and substrate transport became uncoupled. Although ATPase activity was maintained, HorA lost its ability to extrude the prototypical substrate Hoechst33342. Attenuated Total Reflection-Fourier Transform Infrared spectroscopy (ATR-FTIR) revealed that, although the secondary structure of the protein was unaffected, the orientation of the transmembrane helices (TM) was modified by the change in lipid composition. The orientation of the backbone carbonyls indicated that the helices opened wider in PE versus PC-containing liposomes, with 10 degrees difference. This was supported by hydrogen/deuterium exchange studies showing increased protection of the backbone from the solvent in PC-containing liposomes. Electron Paramagnetic Resonance was used to further probe the structural change. In the PC-containing liposomes we observed increased mobility of the spin label in TM4, along with increased exposure to molecular oxygen, used as a hydrophobic quencher. This indicates that the lipid change induced modification of the orientation of TM4, exposing Cys-180 to the lipid phase. The lipid composition of the bilayer thus modulates the structure of HorA, and in turn its ability to extrude its substrates.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.