7KYA

Structure of the S. cerevisiae phosphatidylcholine flippase Dnf2-Lem3 complex in the E2P state

Summary for 7KYA

• Entry DOI: 10.2210/pdb7kya/pdb
• EMDB information: 23068 23069 23070 23071 23072 23073 23074 23075
• Descriptor: Phospholipid-transporting ATPase DNF2, Alkylphosphocholine resistance protein LEM3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: p4 atpase, phosphatidylcholine flippases, translocase
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 234429.40

Authors

Bai, L.,You, Q.,Jain, B.K.,Duan, H.D.,Kovach, A.,Graham, T.R.,Li, H. (deposition date: 2020-12-07, release date: 2021-01-06, Last modification date: 2024-10-23)

Primary citation

Bai, L.,You, Q.,Jain, B.K.,Duan, H.D.,Kovach, A.,Graham, T.R.,Li, H.
Transport mechanism of P4 ATPase phosphatidylcholine flippases.
Elife, 9:-, 2020

PubMed Abstract: 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 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.

PubMed: 33320091
DOI: 10.7554/eLife.62163

Experimental method

ELECTRON MICROSCOPY (3.5 Å)