title: Substrate trajectory through phospholipid-transporting P4-ATPases.
abstract: A difference in the lipid composition between the two leaflets of the same membrane is a relatively simple instance of lipid compositional heterogeneity. The large activation energy barrier for transbilayer movement for some (but not all) membrane lipids creates a regime governed by active transport processes. An early step in eukaryote evolution was the development of a capacity for generating transbilayer compositional heterogeneity far from equilibrium by directly tapping energy from the ATP pool. The mechanism of the P-type ATPases that create lipid asymmetry is well understood in terms of ATP hydrolysis, but the trajectory taken by the phospholipid substrate through the enzyme is a matter of current active research. There are currently three different models for this trajectory, all with support by mutation/activity measurements and analogies with known atomic structures.
authors.affiliation: *Department of Biology and Program in Biochemistry and Biophysics, Amherst College, Amherst, MA 01002, U.S.A.
authors.forename: Patrick
authors.initials: P
authors.lastname: Williamson
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D055162:Biocatalysis; D001692:Biological Transport; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D010743:Phospholipids; D000255:Adenosine Triphosphate; C507517:ATP2B4 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases