Publication Abstract from PubMed
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 beta2 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.
Clathrin adaptors. AP2 controls clathrin polymerization with a membrane-activated switch.,Kelly BT, Graham SC, Liska N, Dannhauser PN, Honing S, Ungewickell EJ, Owen DJ Science. 2014 Jul 25;345(6195):459-63. doi: 10.1126/science.1254836. PMID:25061211[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
