Coat Assembly en GTPases

Vesicle coats are composed of coat protein subunits and adaptor proteins. Adaptor proteins use their PIP-binding domains to interact with PIPs and bend the cytosolic side of the plasma membrane. This allows the coat protein subunits to bind the membrane.

GTP-binding proteins such as Sar1, a small GTPase in the ER, regulate coat protein recruitment to control the location and timing of COPII vesicle formation and fusion. They flip between a GDP-bound inactive state and a GTP-bound active state.

Guanine nucleotide exchange factors or GEFs catalyze the exchange of GDP for GTP in the protein, while GTPase activating proteins or GAPs catalyze the hydrolysis of GTP, thus deactivating the proteins.

The inactive, cytoplasmic Sar1-GDP complex binds Sar1-GEF, located in the ER membrane. As a result, GTP replaces GDP on Sar1, exposing an amphiphilic helix that interacts with the ER membrane.

The ER-bound Sar1-GTP complex recruits COPII adaptor proteins—the Sec23/24 subcomplex. This allows the coat proteins to assemble and initiate vesicle budding.