GIANNAKIS, Eleni, PACIFICO, Jessica, SMITH, David P., HUNG, Lin Wai, MASTERS, Colin L., CAPPAI, Roberto, WADE, John D. and BARNHAM, Kevin J. (2008). Dimeric structures of α-synuclein bind preferentially to lipid membranes. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1778 (4), 1112-1119.Full text not available from this repository.
There is substantial evidence which implicates α-synuclein and its ability to aggregate and bind vesicle membranes as critical factors in the development of Parkinson's disease. In order to investigate the interaction between α-synuclein wild type (Wt) and its familial mutants, A53T and A30P with lipid membranes, we developed a novel lipid binding assay using surface enhanced laser desorption/ionisation-time of flight-mass spectrometry (SELDI-TOF MS). Wt and A53T exhibited similar lipid binding profiles; monomeric species and dimers bound with high relative affinity to the lipid surface, the latter of which exhibited preferential binding. Wt and A53T trimers and tetramers were also detected on the lipid surface. A30P exhibited a unique lipid binding profile; monomeric A30P bound with a low relative affinity, however, the dimeric species of A30P exhibited a higher binding ability. Larger order A30P oligomers were not detected on the lipid surface. Tapping mode atomic force microscopy (AFM) imaging was conducted to further examine the α-synuclein–lipid interaction. AFM analysis revealed Wt and its familial mutants can penetrate lipid membranes or disrupt the lipid and bind the hydrophobic alkyl self-assembled monolayer (SAM) used to form the lipid layer. The profile of these studied proteins revealed the presence of ‘small features’ consistent with the presence of monomeric and dimeric forms of the protein. These data collectively indicate that the dimeric species of Wt and its mutants can bind and cause membrane perturbations.
|Research Institute, Centre or Group:||Biomedical Research Centre|
|Depositing User:||Rebecca Jones|
|Date Deposited:||27 Feb 2012 16:51|
|Last Modified:||27 Feb 2012 16:51|
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