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-Structure paper
Title | Structural basis of the P4B ATPase lipid flippase activity. |
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Journal, issue, pages | Nat Commun, Vol. 12, Issue 1, Page 5963, Year 2021 |
Publish date | Oct 13, 2021 |
Authors | Lin Bai / Bhawik K Jain / Qinglong You / H Diessel Duan / Mehmet Takar / Todd R Graham / Huilin Li / |
PubMed Abstract | P4 ATPases are lipid flippases that are phylogenetically grouped into P4A, P4B and P4C clades. The P4A ATPases are heterodimers composed of a catalytic α-subunit and accessory β-subunit, and the ...P4 ATPases are lipid flippases that are phylogenetically grouped into P4A, P4B and P4C clades. The P4A ATPases are heterodimers composed of a catalytic α-subunit and accessory β-subunit, and the structures of several heterodimeric flippases have been reported. The S. cerevisiae Neo1 and its orthologs represent the P4B ATPases, which function as monomeric flippases without a β-subunit. It has been unclear whether monomeric flippases retain the architecture and transport mechanism of the dimeric flippases. Here we report the structure of a P4B ATPase, Neo1, in its E1-ATP, E2P-transition, and E2P states. The structure reveals a conserved architecture as well as highly similar functional intermediate states relative to dimeric flippases. Consistently, structure-guided mutagenesis of residues in the proposed substrate translocation path disrupted Neo1's ability to establish membrane asymmetry. These observations indicate that evolutionarily distant P4 ATPases use a structurally conserved mechanism for substrate transport. |
External links | Nat Commun / PubMed:34645814 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.08 - 5.64 Å |
Structure data | EMDB-24413, PDB-7rd6: EMDB-24414, PDB-7rd7: EMDB-24415, PDB-7rd8: |
Chemicals | ChemComp-BEF: ChemComp-MG: ChemComp-ALF: ChemComp-ACP: |
Source |
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Keywords | TRANSLOCASE / P4B ATPase lipid flippase |