FIGURE 10.

Hierarchy model of LPH biosynthesis in the ER. The LPH precursor is synthesized at the ER and translocated in the ER lumen starting with the independently folding N-terminal profragment (A). Subsequently, autonomous domain III is synthesized and acquires correct folding independent of other domains (B), whereas homologous domain IV that associates LPH with the membrane is not capable of folding independently (C) and requires the profragment and domain III as folding templates (D). Finally, the correctly folded monomer LPH interacts with another monomer via the correctly folded domain IV to form a transport-competent LPH dimmer that exits the ER and acquires full lactase and phlorizin hydrolase activities (E).