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Transport mechanism of P4 ATPase phosphatidylcholine flippases
The P4 ATPases use ATP hydrolysis to transport large lipid substrates across lipid bilayers. The structures of the endosome- and Golgi-localized phosphatidylserine flippases—such as the yeast Drs2 and human ATP8A1—have recently been reported. However, a substrate-binding site on the cytosolic side h...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773333/ https://www.ncbi.nlm.nih.gov/pubmed/33320091 http://dx.doi.org/10.7554/eLife.62163 |
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author | Bai, Lin You, Qinglong Jain, Bhawik K Duan, H Diessel Kovach, Amanda Graham, Todd R Li, Huilin |
author_facet | Bai, Lin You, Qinglong Jain, Bhawik K Duan, H Diessel Kovach, Amanda Graham, Todd R Li, Huilin |
author_sort | Bai, Lin |
collection | PubMed |
description | The P4 ATPases use ATP hydrolysis to transport large lipid substrates across lipid bilayers. The structures of the endosome- and Golgi-localized phosphatidylserine flippases—such as the yeast Drs2 and human ATP8A1—have recently been reported. However, a substrate-binding site on the cytosolic side has not been found, and the transport mechanisms of P4 ATPases with other substrates are unknown. Here, we report structures of the S. cerevisiae Dnf1–Lem3 and Dnf2–Lem3 complexes. We captured substrate phosphatidylcholine molecules on both the exoplasmic and cytosolic sides and found that they have similar structures. Unexpectedly, Lem3 contributes to substrate binding. The conformational transitions of these phosphatidylcholine transporters match those of the phosphatidylserine transporters, suggesting a conserved mechanism among P4 ATPases. Dnf1/Dnf2 have a unique P domain helix-turn-helix insertion that is important for function. Therefore, P4 ATPases may have retained an overall transport mechanism while evolving distinct features for different lipid substrates. |
format | Online Article Text |
id | pubmed-7773333 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-77733332021-01-04 Transport mechanism of P4 ATPase phosphatidylcholine flippases Bai, Lin You, Qinglong Jain, Bhawik K Duan, H Diessel Kovach, Amanda Graham, Todd R Li, Huilin eLife Biochemistry and Chemical Biology The P4 ATPases use ATP hydrolysis to transport large lipid substrates across lipid bilayers. The structures of the endosome- and Golgi-localized phosphatidylserine flippases—such as the yeast Drs2 and human ATP8A1—have recently been reported. However, a substrate-binding site on the cytosolic side has not been found, and the transport mechanisms of P4 ATPases with other substrates are unknown. Here, we report structures of the S. cerevisiae Dnf1–Lem3 and Dnf2–Lem3 complexes. We captured substrate phosphatidylcholine molecules on both the exoplasmic and cytosolic sides and found that they have similar structures. Unexpectedly, Lem3 contributes to substrate binding. The conformational transitions of these phosphatidylcholine transporters match those of the phosphatidylserine transporters, suggesting a conserved mechanism among P4 ATPases. Dnf1/Dnf2 have a unique P domain helix-turn-helix insertion that is important for function. Therefore, P4 ATPases may have retained an overall transport mechanism while evolving distinct features for different lipid substrates. eLife Sciences Publications, Ltd 2020-12-15 /pmc/articles/PMC7773333/ /pubmed/33320091 http://dx.doi.org/10.7554/eLife.62163 Text en © 2020, Bai et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Bai, Lin You, Qinglong Jain, Bhawik K Duan, H Diessel Kovach, Amanda Graham, Todd R Li, Huilin Transport mechanism of P4 ATPase phosphatidylcholine flippases |
title | Transport mechanism of P4 ATPase phosphatidylcholine flippases |
title_full | Transport mechanism of P4 ATPase phosphatidylcholine flippases |
title_fullStr | Transport mechanism of P4 ATPase phosphatidylcholine flippases |
title_full_unstemmed | Transport mechanism of P4 ATPase phosphatidylcholine flippases |
title_short | Transport mechanism of P4 ATPase phosphatidylcholine flippases |
title_sort | transport mechanism of p4 atpase phosphatidylcholine flippases |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773333/ https://www.ncbi.nlm.nih.gov/pubmed/33320091 http://dx.doi.org/10.7554/eLife.62163 |
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