Fig. 8.

Proposed model for degradation of CD8 chimeras containing defective transmembrane and/or luminal domains. (A) Recognition of proteins containing aberrant TMDs mediates targeting to ERAD ubiquitylation and retrotranslocation complexes, possibly through a lateral gating mechanism. Ubiquitylation of the cytoplasmic domain of the ERAD substrate is then required for retrotranslocation and extraction from the membrane and targeting for degradation. (B) In contrast, proteins containing solely misfolded luminal domains are recognised by luminal ERQC factors and partially retrotranslocated, resulting in ubiquitylation of luminal domains and extraction into the cytoplasm for degradation.