title: Ca(2+) modulating α-synuclein membrane transient interactions revealed by solution NMR spectroscopy.
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.
authors: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors: Zeting
authors: Z
authors: Zhang
authors: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, PR China; Graduate University of Chinese Academy of Sciences, Beijing 100029, PR China.
authors: Chenye
authors: C
authors: Dai
authors: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, PR China; Graduate University of Chinese Academy of Sciences, Beijing 100029, PR China.
authors: Jia
authors: J
authors: Bai
authors: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors: Guohua
authors: G
authors: Xu
authors: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors: Maili
authors: M
authors: Liu
authors: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, PR China. Electronic address: conggangli@wipm.ac.cn.
authors: Conggang
authors: C
authors: Li
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism*; D020404:Glycerophospholipids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C509561:1-palmitoyl-2-oleoyl-phosphatidyl-3-adenosine; C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D020404:Glycerophospholipids; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D051844:alpha-Synuclein; D000241:Adenosine; D002118:Calcium; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
keywords: Ca(2+) function; NMR spectroscopy; Protein membrane transient interaction; α-Synuclein