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...
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| Format: | Article |
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eLife Sciences Publications Ltd
2020-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/62163 |
| _version_ | 1811201422540144640 |
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| author | Lin Bai Qinglong You Bhawik K Jain H Diessel Duan Amanda Kovach Todd R Graham Huilin Li |
| author_facet | Lin Bai Qinglong You Bhawik K Jain H Diessel Duan Amanda Kovach Todd R Graham Huilin Li |
| author_sort | Lin Bai |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T02:20:17Z |
| format | Article |
| id | doaj.art-acb9322c1c9c48e8a853633cc50a4eed |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:20:17Z |
| publishDate | 2020-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-acb9322c1c9c48e8a853633cc50a4eed2022-12-22T03:52:08ZengeLife Sciences Publications LtdeLife2050-084X2020-12-01910.7554/eLife.62163Transport mechanism of P4 ATPase phosphatidylcholine flippasesLin Bai0Qinglong You1Bhawik K Jain2https://orcid.org/0000-0002-1362-6139H Diessel Duan3Amanda Kovach4Todd R Graham5https://orcid.org/0000-0002-3256-2126Huilin Li6https://orcid.org/0000-0001-8085-8928Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University, Beijing, ChinaDepartment of Structural Biology, Van Andel Institute, Grand Rapids, United StatesDepartment of Biological Sciences, Vanderbilt University, Nashville, United StatesDepartment of Structural Biology, Van Andel Institute, Grand Rapids, United StatesDepartment of Structural Biology, Van Andel Institute, Grand Rapids, United StatesDepartment of Biological Sciences, Vanderbilt University, Nashville, United StatesDepartment of Structural Biology, Van Andel Institute, Grand Rapids, United StatesThe 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.https://elifesciences.org/articles/62163P4 ATPaselipid flippasecryoEMstructural biologylipid transport |
| spellingShingle | Lin Bai Qinglong You Bhawik K Jain H Diessel Duan Amanda Kovach Todd R Graham Huilin Li Transport mechanism of P4 ATPase phosphatidylcholine flippases eLife P4 ATPase lipid flippase cryoEM structural biology lipid transport |
| 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 | P4 ATPase lipid flippase cryoEM structural biology lipid transport |
| url | https://elifesciences.org/articles/62163 |
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