title: The newly discovered Parkinson's disease associated Finnish mutation (A53E) attenuates α-synuclein aggregation and membrane binding.
abstract: α-Synuclein (α-Syn) oligomerization and amyloid formation are associated with Parkinson's disease (PD) pathogenesis. Studying familial α-Syn mutants associated with early onset PD has therapeutic importance. Here we report the aggregation kinetics and other biophysical properties of a newly discovered PD associated Finnish mutation (A53E). Our in vitro study demonstrated that A53E attenuated α-Syn aggregation and amyloid formation without altering the major secondary structure and initial oligomerization tendency. Further, A53E showed reduced membrane binding affinity compared to A53T and WT. The present study would help to delineate the role of A53E mutation in early onset PD pathogenesis.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai, India.
authors.forename: Dhiman
authors.initials: D
authors.lastname: Ghosh
authors.forename: Shruti
authors.initials: S
authors.lastname: Sahay
authors.forename: Priyatosh
authors.initials: P
authors.lastname: Ranjan
authors.forename: Shimul
authors.initials: S
authors.lastname: Salot
authors.forename: Ganesh M
authors.initials: GM
authors.lastname: Mohite
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Singh
authors.forename: Saumya
authors.initials: S
authors.lastname: Dwivedi
authors.forename: Edmund
authors.initials: E
authors.lastname: Carvalho
authors.forename: Rinti
authors.initials: R
authors.lastname: Banerjee
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
authors.forename: Samir K
authors.initials: SK
authors.lastname: Maji
mesh_terms: D019943:Amino Acid Substitution; D000682:Amyloid / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002942:Circular Dichroism; D005387:Finland; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008051:Lipid Bilayers; D018625:Microscopy, Atomic Force; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D066263:Protein Aggregation, Pathological; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D020349:Surface Plasmon Resonance; D013499:Surface Properties; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D000682:Amyloid; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; C497604:SNCA protein, human; D051844:alpha-Synuclein