Direct observation of the three regions in α-synuclein that determine its membrane-bound behaviour. Nat Commun 2014 May 29;5:3827
Date
05/30/2014Pubmed ID
24871041Pubmed Central ID
PMC4046108DOI
10.1038/ncomms4827Scopus ID
2-s2.0-84901812732 (requires institutional sign-in at Scopus site) 351 CitationsAbstract
α-synuclein (αS) is a protein involved in neurotransmitter release in presynaptic terminals, and whose aberrant aggregation is associated with Parkinson's disease. In dopaminergic neurons, αS exists in a tightly regulated equilibrium between water-soluble and membrane-associated forms. Here we use a combination of solid-state and solution NMR spectroscopy to characterize the conformations of αS bound to lipid membranes mimicking the composition and physical properties of synaptic vesicles. The study shows three αS regions possessing distinct structural and dynamical properties, including an N-terminal helical segment having a role of membrane anchor, an unstructured C-terminal region that is weakly associated with the membrane and a central region acting as a sensor of the lipid properties and determining the affinity of αS membrane binding. Taken together, our data define the nature of the interactions of αS with biological membranes and provide insights into their roles in the function of this protein and in the molecular processes leading to its aggregation.
Author List
Fusco G, De Simone A, Gopinath T, Vostrikov V, Vendruscolo M, Dobson CM, Veglia GAuthor
Gopinath Tata PhD Assistant Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cell MembraneLipid Bilayers
Lipids
Magnetic Resonance Spectroscopy
Models, Biological
Protein Binding
Protein Structure, Secondary
Unilamellar Liposomes
alpha-Synuclein
