Figure 3. Two models for quality control receptor-substrate targeting to an ER membrane ERAD complex.
A) ERAD receptors recognize aberrant cargo displaying carbohydrate based ERAD signals using their sugar-binding domains (MRH or mannosidase-like domains). The receptor-substrate complex is then delivered to an ERAD complex in the ER membrane consisting of an adapter protein, an E3 ligase and a translocation channel or translocon. B) In an alternative model for selection and delivery, the ERAD receptor selects client proteins based on the folding status of the protein through protein-protein interactions. Once a misfolded protein has been recognized the receptor uses its sugar-binding domain to dock to a glycan on the adapter protein to support delivery of the substrate to the ERAD complex.