Related Experiment Video
Updated: Apr 23, 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
2.2K
α-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation
Jacqueline Burré1, Manu Sharma1, Thomas C Südhof2
1Department of Molecular and Cellular Physiology and.
Summary
Alpha-synuclein multimerizes upon membrane binding, forming ordered complexes. This multimeric, membrane-bound form, not the cytosolic monomer, chaperones soluble NSF attachment protein receptor (SNARE) complex assembly for neuronal function.
Area of Science:
- Neuroscience
- Molecular Biology
- Protein Biochemistry
Background:
- Alpha-synuclein plays dual roles: physiologically chaperoning soluble NSF attachment protein receptor (SNARE) complex assembly and pathologically forming neurotoxic aggregates.
- In neurons, alpha-synuclein exists in equilibrium between cytosolic and membrane-bound states, with distinct conformations.
Purpose of the Study:
- To investigate the oligomeric state of membrane-bound alpha-synuclein.
- To determine whether alpha-synuclein's chaperoning of SNARE complex assembly involves its cytosolic or membrane-bound state.
Main Methods:
- Chemical cross-linking to assess protein multimerization.
- Fluorescence resonance energy transfer (FRET) to analyze intermolecular contacts and conformational changes.
Main Results:
- Alpha-synuclein multimerizes into large, ordered homomeric complexes upon membrane binding.
- Membrane-bound, multimeric alpha-synuclein, but not monomeric cytosolic alpha-synuclein, promotes SNARE complex assembly at the presynaptic plasma membrane.
Conclusions:
- Alpha-synuclein undergoes a folding transition from a monomeric cytosolic form to a multimeric membrane-bound state.
- The multimeric membrane-bound form of alpha-synuclein is the physiologically active chaperone for SNARE complex assembly, potentially protecting against neurodegeneration.
Related Concept Videos
01:43SNAREs and Membrane Fusion
10.3K
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...
10.3K
03:03Amyloid Fibrils
10.1K
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,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
10.1K
02:41Protein Complex Assembly
12.4K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
12.4K
01:26Fusion of Secretory Vesicles with the Plasma Membrane
15.8K
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
15.8K
00:59Mechanisms of Membrane Domain Formation
3.2K
Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with...
Another mechanism for membrane domain formation involves membrane proteins interacting with...
3.2K
01:28Protein Translocation Machinery on the ER Membrane
5.5K
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
5.5K