In eukaryotic cells, intracellular traffic between membrane compartments is mediated by vesicular carriers. Three main types of coated vesicles (COPI-, COPII- and Clathrin-coated vesicles) have been recognized. The COPI-coated vesicles mediate retrograde transport from the Golgi back to the ER and intra-Golgi transport.COPI, a seven subunits complex, can be reversibly dissociated into two subcomplexes: the cage-cap subcomplex which comprise of α-, β’ -, ε -COP and the cargo-binding subcomplex which contains β-, γ-, δ-, ζ-COP . While the crystal structure s of cage-cap subcomplex and γ-, ζ-COP have been better characterized recently, how the structure details of β-, δ-COP is still not clear. In this study, we identified the crystal structure of carboxyl terminus of δ-COP (δ-COP-CTD) at 2.3 Å resolution. Theδ-COP-CTD is almost consist of β-strands just as the AP2-Mu2-CTD. To investigate the molecular mechanism, we have detected the specificity and ability of binding δ-COP-CTD to different ER-resident motifs. Our results demonstrate that interaction with different binding sites of δ-COP may play an important role in sorting process of cargo molecules. We found two residues V210 and F224 are the key interaction sites between δ-COP and its sorting motif DL