Electrogenic reaction step and phospholipid translocation pathway of the mammalian P4-ATPase ATP8A2.

Autor: Tadini-Buoninsegni F; Department of Chemistry 'Ugo Schiff', University of Florence, Sesto Fiorentino, Italy., Mikkelsen SA; Department of Biomedicine, Aarhus University, Denmark., Mogensen LS; Department of Biomedicine, Aarhus University, Denmark., Holm R; Department of Biomedicine, Aarhus University, Denmark., Molday RS; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada.; Department of Ophthalmology and Visual Sciences, Centre for Macular Research, University of British Columbia, Vancouver, Canada., Andersen JP; Department of Biomedicine, Aarhus University, Denmark.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2023 Feb; Vol. 597 (4), pp. 495-503. Date of Electronic Publication: 2022 Aug 09.
DOI: 10.1002/1873-3468.14459
Abstrakt: ATP8A2 is a mammalian P4-ATPase (flippase) that translocates the negatively charged lipid substrate phosphatidylserine from the exoplasmic leaflet to the cytoplasmic leaflet of cellular membranes. Using an electrophysiological method based on solid supported membranes, we investigated the electrogenicity of specific reaction steps of ATP8A2 and explored a potential phospholipid translocation pathway involving residues with positively charged side chains. Changes to the current signals caused by mutations show that the main electrogenic event occurs in connection with the release of the bound phosphatidylserine to the cytoplasmic leaflet and support the hypothesis that the phospholipid interacts with specific lysine and arginine residues near the cytoplasmic border of the lipid bilayer during the translocation and reorientation required for insertion into the cytoplasmic leaflet.
(© 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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