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α-Synuclein Binds Large Unilamellar Vesicles as an Extended Helix†
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This work was supported by a grant from the Ellison Medical Foundation.
, * To whom correspondence should be addressed. 266 Whitney Avenue, P.O. Box 208114, New Haven, CT 06520-8114. Tel: 203-432-5342. Fax: 203-432-5175. E-mail: elizabeth.rhoades@yale.edu.
Section:Abstract
Interactions between the synaptic protein α-Synuclein and cellular membranes may be relevant both to its native function as well as its role in Parkinson’s disease. We use single molecule Förster resonance energy transfer to probe the structure of α-Synuclein bound to detergent micelles and lipid vesicles. We find evidence that it forms a bent-helix when bound to highly curved detergent micelles, whereas it binds more physiological 100 nm diameter lipid vesicles as an elongated helix. Our results highlight the influence of membrane curvature in determining α-Synuclein conformation, which may be important for both its normal and disease-associated functions.
Citing Articles
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This article has been cited by 6 ACS Journal articles (5 most recent appear below).
α-Synuclein Induces Both Positive Mean Curvature and Negative Gaussian Curvature in Membranes
Anthony R. Braun, Eva Sevcsik, Pamela Chin, Elizabeth Rhoades, Stephanie Tristram-Nagle, and Jonathan N. SachsJournal of the American Chemical Society2012 134 (5), 2613-2620α-Synuclein Induces Both Positive Mean Curvature and Negative Gaussian Curvature in Membranes
Anthony R. Braun, Eva Sevcsik, Pamela Chin, Elizabeth Rhoades, Stephanie Tristram-Nagle, and Jonathan N. SachsJournal of the American Chemical Society2012 134 (5), 2613-2620Using a combination of X-ray scattering, fluorescence correlation spectroscopy, coarse-grained molecular dynamics (MD) simulations and potential of mean force calculations, we have explored the membrane remodeling effects of monomeric α-synuclein (αS). ...
Multiparametric Analysis of Intrinsically Disordered Proteins: Looking at Intrinsic Disorder through Compound Eyes
Vladimir N. Uversky and A. Keith DunkerAnalytical Chemistry2012 Article ASAPMultiparametric Analysis of Intrinsically Disordered Proteins: Looking at Intrinsic Disorder through Compound Eyes
Vladimir N. Uversky and A. Keith DunkerAnalytical Chemistry2012 Article ASAPIntrinsically disordered proteins are highly abundant in various proteomes. They are different from ordered proteins at many levels, and their structural and functional characterization requires special experimental and computational tools.
Allostery in a Disordered Protein: Oxidative Modifications to α-Synuclein Act Distally To Regulate Membrane Binding
Eva Sevcsik, Adam J. Trexler, Joanna M. Dunn, and Elizabeth RhoadesJournal of the American Chemical Society2011 133 (18), 7152-7158Allostery in a Disordered Protein: Oxidative Modifications to α-Synuclein Act Distally To Regulate Membrane Binding
Eva Sevcsik, Adam J. Trexler, Joanna M. Dunn, and Elizabeth RhoadesJournal of the American Chemical Society2011 133 (18), 7152-7158Both oxidative stress and aggregation of the protein α-synuclein (aS) have been implicated as key factors in the etiology of Parkinson’s disease. Specifically, oxidative modifications to aS disrupt its binding to lipid membranes, an interaction considered ...
Residue-Specific Fluorescent Probes of α-Synuclein: Detection of Early Events at the N- and C-Termini during Fibril Assembly
Thai Leong Yap, Candace M. Pfefferkorn, and Jennifer C. LeeBiochemistry2011 50 (12), 1963-1965Residue-Specific Fluorescent Probes of α-Synuclein: Detection of Early Events at the N- and C-Termini during Fibril Assembly
Thai Leong Yap, Candace M. Pfefferkorn, and Jennifer C. LeeBiochemistry2011 50 (12), 1963-1965In the Parkinson’s disease-associated state, α-synuclein undergoes large conformational changes, forming ordered, β-sheet-containing fibrils. To unravel the role of specific residues during the fibril assembly process, we prepared single-Cys mutants in ...
Tryptophan Probes at the α-Synuclein and Membrane Interface
Candace M. Pfefferkorn and Jennifer C. LeeThe Journal of Physical Chemistry B2010 114 (13), 4615-4622Tryptophan Probes at the α-Synuclein and Membrane Interface
Candace M. Pfefferkorn and Jennifer C. LeeThe Journal of Physical Chemistry B2010 114 (13), 4615-4622Understanding how environmental factors affect the conformational dynamics of α-synuclein (α-syn) is of great importance because the accumulation and deposit of aggregated α-syn in the brain are intimately connected to Parkinson’s disease etiology. ...
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History
- Published In Issue March 24, 2009
- Article ASAPFebruary 16, 2009
- Just Accepted ManuscriptFebruary 16, 2009
- Received: January 25, 2009
Revised: February 15, 2009
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