TDD structure and three possible mechanisms of CME inhibition. (A) Domain structure of clathrin triskelion. Box indicates the TDD of CHC construct used in this study. (B) TD of CHC (PDB accession no. 1BPO). Four reported binding sites are labeled with different colors, and key functional residues are shown as spheres. (C) Cartoon to illustrate potential TDD inhibitory mechanisms: (1) TDD is incorporated into and destabilizes/weakens the clathrin coat, thus inhibiting CCP maturation; (2) TDD competes for AP2 and inhibits AP2–clathrin interactions; (3) TDD competes for other EAPs required for CCP growth and maturation.