Clathrin adaptors. AP2 controls clathrin polymerization with a membrane-activated switch

Science. 2014 Jul 25;345(6195):459-63. doi: 10.1126/science.1254836.


Clathrin-mediated endocytosis (CME) is vital for the internalization of most cell-surface proteins. In CME, plasma membrane-binding clathrin adaptors recruit and polymerize clathrin to form clathrin-coated pits into which cargo is sorted. Assembly polypeptide 2 (AP2) is the most abundant adaptor and is pivotal to CME. Here, we determined a structure of AP2 that includes the clathrin-binding β2 hinge and developed an AP2-dependent budding assay. Our findings suggest that an autoinhibitory mechanism prevents clathrin recruitment by cytosolic AP2. A large-scale conformational change driven by the plasma membrane phosphoinositide phosphatidylinositol 4,5-bisphosphate and cargo relieves this autoinhibition, triggering clathrin recruitment and hence clathrin-coated bud formation. This molecular switching mechanism can couple AP2's membrane recruitment to its key functions of cargo and clathrin binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 2 / chemistry*
  • Adaptor Protein Complex beta Subunits / chemistry*
  • Cell Membrane / chemistry*
  • Clathrin / chemistry*
  • Endocytosis
  • Humans
  • Phosphatidylinositol 4,5-Diphosphate / chemistry
  • Polymerization*


  • Adaptor Protein Complex 2
  • Adaptor Protein Complex beta Subunits
  • Clathrin
  • Phosphatidylinositol 4,5-Diphosphate

Associated data

  • PDB/4UQI