Fig. 3. Enthoprotin interactions at the TGN. TGN clathrin adaptors AP-1 and GGA2 are targeted to the membrane through interactions with ARF1-GTP, where they bind peptide motifs present in the cytoplasmic tails of sorting receptors. AP-1 is composed of four distinct subunits: -, ß1-, µ1- and 1-adaptin. - and ß1-adaptin each contains a globular C-terminal region referred to as an ear domain. PtdIns4P binding also contributes to the membrane recruitment of AP-1. GGA2 is a monomeric adaptor containing VHS (Vps27p, Hrs, STAM), GAT (GGA and TOM) and GAE (-adaptin ear) domains. The ear domains are linked to the adaptors via flexible hinge domains. Both adaptors recruit clathrin triskelia to the TGN membrane via clathrin-binding motifs present in the hinge. Enthoprotin is targeted to the TGN through a combination of interactions including ENTH domain binding to PtdIns4P and additional interactions in the C-terminal region. Its unstructured C-terminal tail is involved in interactions with GGA2 and AP-1 through -ear/GAE-domain-binding motifs with the sequence GFADF and DFGDW. Enthoprotin also binds to the terminal domain (TD) of the clathrin heavy chain via clathrin-binding motifs LVDLF and LFDLM and can contribute to clathrin assembly. The ENTH domain could be involved in the production of membrane curvature through membrane insertion.