8.A.152.1.11
Interleukin-7 receptor, IL7R, subunit alpha; it is of 459 aas with 2 TMSs, one N-terminal, and one at about residue 250. It also acts as a receptor for thymic stromal lymphopoietin (TSLP), and may play a role in osteoporosis (Wu et al. 2023). It is found in the clathrin-coated endocytic vesicle membrane. During cotranslational translocation, the signal peptide of a nascent chain binds the Sec61 translocon to initiate protein transport through the ER membrane. The cryo-EM structure of ribosome-Sec61 shows binding of an ordered heterotetrameric translocon-associated protein (TRAP) complex, in which TRAP-gamma is anchored at two adjacent positions of 28S ribosomal RNA and interacts with ribosomal protein L38 and Sec61alpha/gamma. Four TMSs of TRAP-gamma cluster with one C-terminal helix of each alpha, beta, and delta subunit. The seven TMS bundle helps position a crescent-shaped trimeric TRAP-alpha/beta/delta core in the ER lumen, facing the Sec61 channel. A cyclotriazadisulfonamide derivative CK147 is a translocon inhibitor. A structure of ribosome-Sec61-CK147 reveals CK147 binding the channel and interacting with the plug helix from the lumenal side. The CK147 resistance mutations surround the inhibitor. These structures help in understanding TRAP functions (Pauwels et al. 2023).