Lipid interactions enhance activation and potentiation of cystic fibrosis transmembrane conductance regulator (CFTR). Chin, S., Ramjeesingh, M., Hung, M., Ereño-Oreba, J., Ing, C., Zeng, Z., Cui, H., Pomès, R., Julien, J., & Bear, C. 2018.
abstract   bibtex   
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. The recent cryo-electron microscopy structures of phosphorylated, ATP-bound CFTR in detergent micelles failed to reveal an open anion conduction pathway as expected on the basis of previous functional studies in biological membranes. We tested the hypothesis that interaction of CFTR with lipids is important for opening of its channel. Interestingly, molecular dynamics studies revealed that phospholipids associate with regions of CFTR proposed to contribute to its channel activity. More directly, we found that CFTR purified together with associated lipids using the amphipol: A8-35, exhibited higher rates of catalytic activity, channel activation and potentiation using ivacaftor, than did CFTR purified in detergent. Catalytic activity in CFTR detergent micelles was partially rescued by addition of phospholipids plus cholesterol, arguing that these lipids contribute directly to its modulation. In summary, these studies highlight the importance of lipids in regulated CFTR channel activation and potentiation.
@misc{
 title = {Lipid interactions enhance activation and potentiation of cystic fibrosis transmembrane conductance regulator (CFTR)},
 type = {misc},
 year = {2018},
 source = {bioRxiv},
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 id = {7f30375a-ce8f-3955-b08b-5497c83e956f},
 created = {2020-10-27T23:59:00.000Z},
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 last_modified = {2020-10-29T15:44:35.682Z},
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 abstract = {The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. The recent cryo-electron microscopy structures of phosphorylated, ATP-bound CFTR in detergent micelles failed to reveal an open anion conduction pathway as expected on the basis of previous functional studies in biological membranes. We tested the hypothesis that interaction of CFTR with lipids is important for opening of its channel. Interestingly, molecular dynamics studies revealed that phospholipids associate with regions of CFTR proposed to contribute to its channel activity. More directly, we found that CFTR purified together with associated lipids using the amphipol: A8-35, exhibited higher rates of catalytic activity, channel activation and potentiation using ivacaftor, than did CFTR purified in detergent. Catalytic activity in CFTR detergent micelles was partially rescued by addition of phospholipids plus cholesterol, arguing that these lipids contribute directly to its modulation. In summary, these studies highlight the importance of lipids in regulated CFTR channel activation and potentiation.},
 bibtype = {misc},
 author = {Chin, S. and Ramjeesingh, M. and Hung, M. and Ereño-Oreba, J. and Ing, C. and Zeng, Z.W. and Cui, H. and Pomès, R. and Julien, J.-P. and Bear, C.E.}
}

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