Clathrin is a major cytosolic coat protein in pits and vesicles originating from the plasma membrane and the trans-Golgi network. In receptor-mediated endocytosis, receptor proteins are englufed by clathrin-coated vesicles. Clathrin is composed of three heavy chains and three light chains which associate non-covalently to form a triskelion structure. Clathrin heavy chain (HC) is composed of a terminal globular domain, a distal segment and a proximal segment containing a light chain binding site. The proximal segment of the Clathrin HC protein is essential for interactions between clathrin heavy chains and light chains which result in the formation of the triskelion structure.