Abstract

Clathrin is the main component of the coat that decorates the cytosolic face of carrier vesicles mediating protein and lipid transport in the endocytic and late secretory pathways. In vivo the multimerisation of the clathrin heterohexamer (known as triskelion) and the clathrin-mediated vesicular trafficking are regulated through a complex network of interactions involving clathrin and a number of accessory proteins.
Clathrin boxes are 5-residue-motifs found on cargo adaptor proteins, mostly near their C-terminus or central region. They are found in a large variety of accessory proteins involved in endocytosis and vesicular trafficking (specific adaptors like beta-arrestin and more general adaptor proteins like AP complexes). Unfolded flexible regions or hinges can display multiple copies of the motif, sometime belonging to different subtypes. This organisation is believed to ensure a complex, ajustable network of "weak" cooperative interactions, with the affinity between members defined by the number of motifs they possess. Extended peptides could also promote clathrin assembly by bridging the heavy chains of clathrin molecules engaged in an assembled coat. Clathin box motifs interact with the N-terminus of Clathrin heavy chain, with the so called beta-propeller structure.