A novel all helix fold of the AP180 amino-terminal domain for phosphoinositide binding and clathrin assembly in synaptic vesicle endocytosis

Clathrin-mediated endocytosis plays a major role in retrieving synaptic Ves icles from the plasma membrane following exocytosis. This endocytic process requires AP180 (or a homolog), which promotes the assembly and restricts t he size of clathrin-coated vesicles. The highly conserved 33 kDa amino-term inal domain of AP180 plays a critical role in binding to phosphoinositides and in regulating the clathrin assembly activity of AP180. The crystal stru cture of the aminoterminal domain reported herein reveals a never fold cons isting of a large double layer of sheets of ten alpha helices and a unique site for binding phosphoinositides. The finding that the clathrin-box motif is mostly buried and lies in a helix indicates a different site and mechan ism for binding of the domain to clathrins than previously assumed.