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Structural basis of the P4B ATPase lipid flippase activity.
- Source :
- Nature Communications; 10/13/2021, Vol. 12 Issue 1, p1-12, 12p
- Publication Year :
- 2021
-
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. The P4 ATPase lipid flippases play a crucial role in membrane biogenesis. Here the authors report the structure of the monomeric P4B ATPase Neo1 in several states, clarifying the mechanism of substrate transport. [ABSTRACT FROM AUTHOR]
- Subjects :
- ADENOSINE triphosphatase
HETERODIMERS
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 153011208
- Full Text :
- https://doi.org/10.1038/s41467-021-26273-0