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We will determine how PI4,5P2, cargo, clathrin and endocytic accessory factor binding to AP2, as well as phosphorylation events trigger conformational changes in AP2 to regulate initial events in clathrin coated pit (CCP) assembly, stabilization of nascent CCPs and their maturation.
Class 5 sequence variations produce receptors that bind ligands in coated pits but fail to release them at acidic pH in endosomes, and thus do not recycle to the cell surface (13).
The remaining domains of the LDL receptor provide the sites for sugar attachment; a segment that goes across the cell membrane; and a stretch of amino acids that falls on the cytoplasmic side of the membrane and anchors the receptors to their characteristic surface sites, structures called coated pits.