Related Experiment Video
Updated: Jun 25, 2026
07:56
Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time
Published on: May 30, 2021
Alpha-synuclein binds large unilamellar vesicles as an extended helix
Adam J Trexler1, Elizabeth Rhoades
1Department of Molecular Biophysics and Biochemistry, Yale University, P.O. Box 208114, New Haven, Connecticut 06520, USA.
Biochemistry
|February 18, 2009
Summary
Alpha-Synuclein
Area of Science:
- Biochemistry
- Neuroscience
- Molecular Biology
Background:
- Interactions between alpha-Synuclein and cellular membranes are crucial for its function and role in Parkinson's disease.
- Understanding alpha-Synuclein's structure and membrane binding is key to deciphering its involvement in neurodegenerative disorders.
Purpose of the Study:
- To investigate the structural conformation of alpha-Synuclein when interacting with membranes of varying curvature.
- To elucidate how membrane properties influence alpha-Synuclein's structure and potential function.
Main Methods:
- Utilized single-molecule Förster resonance energy transfer (smFRET) to analyze alpha-Synuclein structure.
- Studied alpha-Synuclein binding to detergent micelles (high curvature) and lipid vesicles (100 nm diameter, physiological curvature).
Main Results:
- Alpha-Synuclein adopts a bent-helix conformation when bound to highly curved detergent micelles.
- When bound to physiological lipid vesicles, alpha-Synuclein adopts an elongated helical structure.
- Membrane curvature significantly dictates the conformational state of alpha-Synuclein.
Conclusions:
- Membrane curvature is a critical factor influencing alpha-Synuclein's structure.
- The distinct conformations observed may have implications for alpha-Synuclein's normal physiological roles and its pathological involvement in Parkinson's disease.
More Related Videos
Related Concept Videos
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:38Intralumenal Vesicles and Multivesicular Bodies
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
01:12Clathrin Coated Vesicles
Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
01:33Overview of Secretory Vesicles
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
01:45Vesicular Tubular Clusters
After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
With the help of motor proteins such...
01:43SNAREs and Membrane Fusion
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...