Versatile membrane deformation potential of activated pacsin
Shih Lin Goh1, Qi Wang, Laura J Byrnes
1Department of Molecular Medicine, Cornell University, Ithaca, New York, United States of America.
Plos One
|December 14, 2012
Summary
Pacsin-1 protein, crucial for cell membrane dynamics, becomes highly active when interacting with dynamin. This interaction enables pacsin-1 to generate distinct membrane shapes and small vesicles, aiding in cellular processes.
Area of Science:
- Cell Biology
- Molecular Biology
- Biophysics
Background:
- Endocytosis is vital for cell signaling and membrane trafficking, involving proteins like dynamin and the actin cytoskeleton.
- Pacsin, an F-BAR domain protein, influences membrane curvature and morphology during vesicle formation.
- Full-length pacsin isoform 1 (pacsin-1) exhibits lower activity than its isolated F-BAR domain, suggesting autoinhibition by its SH3 domain.
Purpose of the Study:
- To investigate the mechanism of pacsin-1 autoinhibition and its release.
- To characterize the membrane deformation activity of activated pacsin-1 in complex with dynamin.
- To explore the influence of liposome preparation methods on BAR domain protein activity.
Main Methods:
- Biochemical assays to study pacsin-1 and dynamin-1 interactions.
- In vitro experiments using liposomes to observe membrane morphology changes.
- Theoretical free energy calculations to model protein-membrane interactions.
Main Results:
- Binding of pacsin-1 to dynamin-1's proline-rich domain releases autoinhibition, revealing potent membrane deformation activity.
- Activated pacsin-1 generates distinct membrane morphologies, including small, homogenous vesicles under specific conditions.
- Liposome preparation methods significantly impact membrane deformation by BAR domain proteins and pacsin-1's activation barriers.
Conclusions:
- Pacsin-1's activity is regulated by intramolecular interactions, which can be overcome by dynamin binding.
- The study reveals a versatile role for pacsin-1 in cellular membrane sculpting, influenced by protein structure and membrane properties.
- Bimodality in the protein-membrane system may explain the coexistence of different membrane structures observed in vitro.
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