Constitutive phospholipid scramblase activity of a G protein-coupled receptor. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cattle
  • Opsins
  • Protein Conformation
  • Receptors, Adenosine A2

MeSH Major

  • Phospholipid Transfer Proteins
  • Receptors, Adrenergic, beta-2
  • Rhodopsin

abstract

  • Opsin, the rhodopsin apoprotein, was recently shown to be an ATP-independent flippase (or scramblase) that equilibrates phospholipids across photoreceptor disc membranes in mammalian retina, a process required for disc homoeostasis. Here we show that scrambling is a constitutive activity of rhodopsin, distinct from its light-sensing function. Upon reconstitution into vesicles, discrete conformational states of the protein (rhodopsin, a metarhodopsin II-mimic, and two forms of opsin) facilitated rapid (>10,000 phospholipids per protein per second) scrambling of phospholipid probes. Our results indicate that the large conformational changes involved in converting rhodopsin to metarhodopsin II are not required for scrambling, and that the lipid translocation pathway either lies near the protein surface or involves membrane packing defects in the vicinity of the protein. In addition, we demonstrate that β2-adrenergic and adenosine A2A receptors scramble lipids, suggesting that rhodopsin-like G protein-coupled receptors may play an unexpected moonlighting role in re-modelling cell membranes.

publication date

  • October 8, 2014

has subject area

  • Animals
  • Cattle
  • Opsins
  • Phospholipid Transfer Proteins
  • Protein Conformation
  • Receptors, Adenosine A2
  • Receptors, Adrenergic, beta-2
  • Rhodopsin

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4198942

Digital Object Identifier (DOI)

  • 10.1038/ncomms6115

PubMed ID

  • 25296113

Additional Document Info

start page

  • 5115

volume

  • 5