Coarse-Grained Model of SNARE-Mediated Docking.
Biophys J
; 108(9): 2258-69, 2015 May 05.
Article
en En
| MEDLINE
| ID: mdl-25954883
ABSTRACT
Synaptic transmission requires that vesicles filled with neurotransmitter molecules be docked to the plasma membrane by the SNARE protein complex. The SNARE complex applies attractive forces to overcome the long-range repulsion between the vesicle and membrane. To understand how the balance between the attractive and repulsive forces defines the equilibrium docked state we have developed a model that combines the mechanics of vesicle/membrane deformation with an apparently new coarse-grained model of the SNARE complex. The coarse-grained model of the SNARE complex is calibrated by comparison with all-atom molecular dynamics simulations as well as by force measurements in laser tweezer experiments. The model for vesicle/membrane interactions includes the forces produced by membrane deformation and hydration or electrostatic repulsion. Combining these two parts, the coarse-grained model of the SNARE complex with membrane mechanics, we study how the equilibrium docked state varies with the number of SNARE complexes. We find that a single SNARE complex is able to bring a typical synaptic vesicle to within a distance of â¼ 3 nm from the membrane. Further addition of SNARE complexes shortens this distance, but an overdocked state of >4-6 SNAREs actually increases the equilibrium distance.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas SNARE
/
Simulación del Acoplamiento Molecular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biophys J
Año:
2015
Tipo del documento:
Article
Pais de publicación:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA