Seminar: Cargo binding triggers polymerization of a clathrin-independent vesicle coat

Movement between membrane-bound organelles requires budding and fusion of coated vesicles. While clathrin has received decades of research, many “orphan” vesicles coats that do not rely on clathrin have received relatively little investigation, despite their strong link to disease. One such coat, AP-3, mediates cargo sorting in the endosome and its mutation causes a multitude of lysosomal storage diseases. By reconstituting AP-3 assembly intermediates on lipid nanodiscs, and determining their structure via cryo-EM, we have determined the stepwise assembly of a clathrin-independent vesicle coat. We show that binding to trans-membrane cargo induces a large conformational changes that triggers higher order assembly of the coat. We propose that cargo identity induces specific structural changes that control the timing and specificity of transport.