Clathrin Assembly Regulated by Adaptor Proteins in Coarse-Grained Models.

Area of Science:

• Biophysics
• Cell Biology
• Computational Biology

Background:

• Clathrin-mediated endocytosis relies on clathrin triskelia assembling into polyhedral cages.
• Adaptor proteins (APs) are known regulators of this clathrin assembly process.
• The precise mechanisms by which APs influence clathrin coat formation remain incompletely understood.

Purpose of the Study:

• To investigate the role of adaptor proteins (APs) in regulating clathrin assembly.
• To model the collective aggregation behavior of clathrin and AP2 using computational approaches.
• To elucidate the contribution of AP mechanical properties to clathrin cage formation.

Main Methods:

• Development of coarse-grained models for clathrin and AP2.
• Utilized Monte Carlo simulations with a click interaction to study aggregation.
• Formulated a statistical-mechanical theory to analyze clathrin assembly behavior.

Main Results:

• Phase diagrams revealed that the mechanical properties of the AP disordered linker segment are critical.
• Simulations showed good agreement with existing experimental data for clathrin assembly.
• Identified conditions under which APs can both promote and inhibit clathrin cage formation.

Conclusions:

• The mechanical properties of adaptor protein linkers significantly influence clathrin coat assembly.
• A statistical-mechanical framework accurately describes clathrin assembly dynamics.
• Adaptor proteins exhibit context-dependent regulation, capable of both facilitating and hindering clathrin cage formation.