FIG. 3.

Disulfide disruption as a prerequisite for ERAD. (1) Disruption of disulfide bonds within an ER protein leads to more complete unfolding and exposure of hydrophobic patches. This increased hydrophobicity allows for the recruitment of factors involved in selecting substrates for ERAD. (2) Removal of disulfide bonds can increase the efficiency of ERAD. Substrates that are erroneously multimerized by disulfide bonds are disrupted to allow more complete unfolding and processing by ERAD membrane machinery including the retro-translocation channel. (3) Disulfide bond disruption can allow auto-catalytic processing of Hedgehog (Hh). This processing produces an unused C-terminal fragment, which is constitutively degraded by an ERAD pathway.