7RD8

Structure of the S. cerevisiae P4B ATPase lipid flippase in the E1-ATP state

Summary for 7RD8

• Entry DOI: 10.2210/pdb7rd8/pdb
• EMDB information: 24413 24414 24415
• Descriptor: Probable phospholipid-transporting ATPase NEO1, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, MAGNESIUM ION (3 entities in total)
• Functional Keywords: p4b atpase lipid flippase, translocase
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Total number of polymer chains: 1
• Total formula weight: 130893.00

Authors

Bai, L.,Jain, B.K.,You, Q.,Duan, H.D.,Graham, T.R.,Li, H. (deposition date: 2021-07-09, release date: 2021-09-29, Last modification date: 2025-05-28)

Primary citation

Bai, L.,Jain, B.K.,You, Q.,Duan, H.D.,Takar, M.,Graham, T.R.,Li, H.
Structural basis of the P4B ATPase lipid flippase activity.
Nat Commun, 12:5963-5963, 2021

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 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.

PubMed: 34645814
DOI: 10.1038/s41467-021-26273-0

Experimental method

ELECTRON MICROSCOPY (5.64 Å)