Fig. 1. Structure and topology of ERdj1 and ERdj2.

Upper line: Computational analyses of the structure of ERdj1 predicts a cleavable signal peptide and three transmembrane domains (green lines). Green lines in brackets indicate that the existence of the transmembrane domain was not confirmed experimentally. The probability of signal sequence cleavage (arrow) of ERdj1 is calculated to be 97%. Experimental data show that the first predicted transmembrane domain, which is located within the signal sequence, is cleaved upon translocation of ERdj1 into the ER. ERdj1 is anchored within the membrane of the endoplasmic reticulum by the second predicted transmembrane domain while the third predicted transmembrane domain is not used in vivo resulting in a cytosolically localized C-terminus, which interacts with the ribosome to inhibit the initiation of translation [9]. When the J-domain binds to BiP this inhibition is released and cotranslational translocation of specific proteins proceeds [9, 12, 14]. Lower line: Computational analyses of ERdj2 predicts three transmembrane regions, the orientation is likewise possible with the C-terminus either intraluminal or cytosolic. No signal sequence is identified by computational programs. Experimental data confirm two of the predicted transmembrane domains resulting in a topology with the N- and C-terminus facing the cytosol and the J-domain being located in the lumen of the ER. The C-terminus of ERdj2 interacts with Sec62 and inhibits the translation of target proteins [18]. The J-domain of ERdj2 can bind to BiP in the presence of ATP and stimulate its ATPase activity [17] releasing the translational block at the ribosomal tunnel exit.