The structure and function of the beta2-adaptin appendage domain

Abstract

The heterotetrameric AP2 adaptor (α, β2, μ2 and σ2 subunits) plays a central role in clathrin‐mediated endocytosis. We present the protein recruitment function and 1.7 Å resolution structure of its β2‐appendage domain to complement those previously determined for the μ2 subunit and α appendage. Using structure‐directed mutagenesis, we demonstrate the ability of the β2 appendage alone to bind directly to clathrin and the accessory proteins AP180, epsin and eps15 at the same site. Clathrin polymerization is promoted by binding of clathrin simultaneously to the β2‐appendage site and to a second site on the adjacent β2 hinge. This results in the displacement of the other ligands from the β2 appendage. Thus clathrin binding to an AP2–accessory protein complex would cause the controlled release of accessory proteins at sites of vesicle formation.