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Stimulation of α-synuclein amyloid formation by phosphatidylglycerol micellar tubules
| Content Provider | Scilit |
|---|---|
| Author | Jiang, Zhiping Flynn, Jessica Teague, Walter E. Gawrisch, Klaus Lee, Jennifer C. |
| Copyright Year | 2018 |
| Description | Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes α-Synuclein (α-Syn) is a presynaptic protein that is accumulated in its amyloid form in the brains of Parkinson's patients. Although its biological function remains unclear, α-syn has been suggested to bind to synaptic vesicles and facilitate neurotransmitter release. Recently, studies have found that α-syn induces membrane tubulation, highlighting a potential mechanism for α-syn to stabilize highly curved membrane structures which could have both functional and dysfunctional consequences. To understand how membrane remodeling by α-syn affects amyloid formation, we have studied the α-syn aggregation process in the presence of phosphatidylglycerol (PG) micellar tubules, which were the first reported example of membrane tubulation by α-syn. Aggregation kinetics, β-sheet content, and macroscopic protein-lipid structures were observed by Thioflavin T fluorescence, circular dichroism spectroscopy and transmission electron microscopy, respectively. Collectively, the presence of PG micellar tubules formed at a stochiometric (L/P = 1) ratio was found to stimulate α-syn fibril formation. Moreover, transmission electron microscopy and solid-state nuclear magnetic resonance spectroscopy revealed the co-assembly of PG and α-syn into fibril structures. However, isolated micellar tubules do not form fibrils by themselves, suggesting an important role of free α-syn monomers during amyloid formation. In contrast, fibrils did not form in the presence of excess PG lipids (≥L/P = 50), where most of the α-syn molecules are in a membrane-bound α-helical form. Our results provide new mechanistic insights into how membrane tubules modulate α-syn amyloid formation and support a pivotal role of protein-lipid interaction in the dysfunction of α-syn. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125227/pdf |
| Ending Page | 1847 |
| Page Count | 8 |
| Starting Page | 1840 |
| ISSN | 00052736 |
| DOI | 10.1016/j.bbamem.2018.02.025 |
| Journal | Biochimica et Biophysica Acta (BBA) - Biomembranes |
| Issue Number | 9 |
| Volume Number | 1860 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2018-09-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes Biochemistry and Molecular Biology Circular Dichroism Membrane Remodeling Parkinson's Disease Protein-lipid Interaction Thioflavin T Transmission Electron Microscopy |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Biophysics |
