Specific mutations in mammalian P4-ATPase ATP8A2 catalytic subunit entail differential glycosylation of the accessory CDC50A subunit

FEBS Lett. 2015 Dec 21;589(24 Pt B):3908-14. doi: 10.1016/j.febslet.2015.11.031. Epub 2015 Nov 22.

Abstract

P4-ATPases, or flippases, translocate phospholipids between the two leaflets of eukaryotic biological membranes. They are essential to the physiologically crucial phospholipid asymmetry and involved in severe diseases, but their molecular structure and mechanism are still unresolved. Here, we show that in an extensive mutational alanine screening of the mammalian flippase ATP8A2 catalytic subunit, five mutations stand out by leading to reduced glycosylation of the accessory subunit CDC50A. These mutations may disturb the interaction between the subunits.

Keywords: CDC50; Flippase; Interaction site; Membrane transport; P-type ATPase; TMEM30.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Catalytic Domain / genetics*
  • Cattle
  • Cell Membrane / metabolism
  • Glycosylation
  • Membrane Proteins / metabolism*
  • Molecular Dynamics Simulation
  • Mutation*
  • Phospholipid Transfer Proteins / chemistry*
  • Phospholipid Transfer Proteins / genetics
  • Phospholipid Transfer Proteins / metabolism*
  • Protein Subunits / metabolism*

Substances

  • Membrane Proteins
  • Phospholipid Transfer Proteins
  • Protein Subunits