FIG. 5.
ER events promoting cholera toxin subunit A 1 (CTA1) retro-translocation. Step 1. CT is targeted to the Derlin-1/Hrd1 complex via cholera toxin subunit B (CTB). Step 2.The CTA disulfide bond is reduced by an unidentified reductase to generate CTA1. Step 3. CTA1 is then unfolded by the bb′a′ domains of reduced protein disulfide isomerase (PDI) attached to the Derlin-1/Hrd1 complex. Step 4. Ero1α oxidizes PDI's a′ domain. Step 5. Oxidized PDI releases CTA1 into the retro-translocation channel and detaches from the Derlin-1/Hrd1 complex. Step 6. CTA1 avoids proteasomal degradation and refolds spontaneously in the cytosol to elicit its toxic effects.