Figure 6.

A model showing the roles of the C-terminal tail in membrane protein insertion and assembly. The C-TMD with a short tail is post-translationally recognized by the Sec61 translocon because the translation is terminated before the C-TMD contact the Sec61 translocon. The insufficiently hydrophobic C-TMD of WRB is transiently retained by the Sec61 translocon. This retention provides a time window to assemble with CAML, which is likely associated with the Sec61 translocon through its C-TMD or TMD2 (not shown). The topology of unassembled CAML is adopted from recent studies (25, 26). If the Sec61-retained TMD fails to be assembled with a partner TMD, it slowly translocates through the translocon into the ER lumen. The translocated TMD is recognized by the ERAD pathway for proteasomal degradation.