Using Site-Specific Vibrational Spectroscopy to Determine Structure of Membrane-Bound N-Terminally Acetylated Alpha-Synuclein
نویسندگان
چکیده
منابع مشابه
Membrane-bound structure and energetics of alpha-synuclein.
Aggregation and fibrillation of alpha-synuclein bound to membranes are believed to be involved in Parkinson's and other neurodegenerative diseases. On SDS micelles, the N-terminus of alpha-synuclein forms two curved helices linked by a short loop. However, its structure on lipid bilayers has not been experimentally resolved. Using MD simulations with an implicit membrane model we show here that...
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alpha-Synuclein is known to play a causative role in Parkinson disease. Although its physiological functions are not fully understood, alpha-synuclein has been shown to interact with synaptic vesicles and modulate neurotransmitter release. However, the structure of its physiologically relevant membrane-bound state remains unknown. Here we developed a site-directed spin labeling and EPR-based ap...
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Growing evidence supports a link between brain copper homeostasis, the formation of alpha-synuclein (AS)-copper complexes, and the development of Parkinson disease (PD). Recently it was demonstrated that the physiological form of AS is N-terminally acetylated (AcAS). Here we used NMR spectroscopy to structurally characterize the interaction between Cu(I) and AcAS. We found that the formation of...
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Many of the proposed physiological functions of -synuclein, a protein involved in the pathogenesis of Parkinson’s disease, are related to its ability to interact with phospholipids. To better understand the conformational changes that occur upon membrane binding of monomeric -synuclein, we performed EPR analysis of 47 singly labeled -synuclein derivatives. We show that membrane interaction is m...
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While most forms of Parkinson's Disease (PD) are sporadic in nature, a small percentage of PD have genetic causes as first described for dominant, single base pair changes as well as duplication and triplication in the α-synuclein gene. The α-synuclein gene encodes a 140 amino acid residue protein that interacts with a variety of organelles including synaptic vesicles, lysosomes, endoplasmic re...
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ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2019
ISSN: 0006-3495
DOI: 10.1016/j.bpj.2018.11.1907