Ca(2+) modulating α-synuclein membrane transient interactions revealed by solution NMR spectroscopy

Biochim Biophys Acta. 2014 Mar;1838(3):853-8. doi: 10.1016/j.bbamem.2013.11.016. Epub 2013 Dec 4.

Abstract

α-Synuclein is involved in Parkinson's disease and its interaction with cell membrane is crucial to its pathological and physiological functions. Membrane properties, such as curvature and lipid composition, have been shown to affect the interactions by various techniques, but ion effects on α-synuclein membrane interactions remain elusive. Ca(2+) dynamic fluctuation in neurons plays important roles in the onset of Parkinson's disease and its influx is considered as one of the reasons to cause cell death. Using solution Nuclear Magnetic Resonance (NMR) spectroscopy, here we show that Ca(2+) can modulate α-synuclein membrane interactions through competitive binding to anionic lipids, resulting in dissociation of α-synuclein from membranes. These results suggest a negative modulatory effect of Ca(2+) on membrane mediated normal function of α-synuclein, which may provide a clue, to their dysfunction in neurodegenerative disease.

Keywords: Ca(2+) function; NMR spectroscopy; Protein membrane transient interaction; α-Synuclein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / chemistry
  • Adenosine / metabolism
  • Apolipoprotein A-I / metabolism
  • Calcium / pharmacology*
  • Cell Membrane / metabolism*
  • Glycerophospholipids / chemistry
  • Glycerophospholipids / metabolism
  • Humans
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism
  • Magnetic Resonance Spectroscopy*
  • Phosphatidylcholines / chemistry
  • Phosphatidylcholines / metabolism
  • Protein Binding
  • alpha-Synuclein / chemistry*
  • alpha-Synuclein / metabolism*

Substances

  • 1-palmitoyl-2-oleoyl-phosphatidyl-3-adenosine
  • APOA1 protein, human
  • Apolipoprotein A-I
  • Glycerophospholipids
  • Lipid Bilayers
  • Phosphatidylcholines
  • alpha-Synuclein
  • Adenosine
  • Calcium
  • 1-palmitoyl-2-oleoylphosphatidylcholine