Figure 9. Model of bidirectional intermolecular interactions of misfolded and native proteins.

Within the ER, many secretory proteins, including proinsulin and Tg, form homodimers. When mutant and WT alleles from the same gene cross-dimerize, there may be several outcomes, two of which are summarized in the figure. The WT gene product can assist the mutant partner to exit the ER, or the mutant protein can block anterograde transport of the WT protein. Among other protein-specific and general factors involved, the relative concentrations (i.e., stoichiometric ratio) of the 2 dimerization partners also contribute to the outcome, with lower WT/mutant ratios resulting in greater ER retention and higher WT/mutant ratios resulting in enhanced forward transport.