Figure 1.

Cellular location, membrane topology, and extramembrane domains of S2P, SpoIVFB, and RseP. A) Human S2P is located in the membranes of the Golgi apparatus and has 8 predicted TMSs of which TMSs 4–6 make up the conserved core (orange). The positions of a Ser-rich loop, the HEXXH motif, the lumenal PDZ domain with its Cys-rich insert, and D467 in TMS 6 are shown. When substrate SREBPs are transported from the endoplasmic reticulum to the Golgi apparatus, S1P cleaves a lumenal loop, allowing S2P to cleave TMS 1 and release the N-terminal basic helix-loop-helix (bHLH) leucine-zipper (zip) domain into the cytosol. The bHLH-zip domain enters the nucleus and activates transcription. The regulatory domain (Reg.) interacts with SCAP (not shown). B) SpoIVFB is located in the outermost membrane surrounding the forespore during B. subtilis sporulation. Features analogous to those noted above in S2P are indicated. The CBS domain is in the mother cell, as is most of Pro-σ^K, whose pro-sequence is depicted to interact peripherally and loop into the membrane, although this is speculative. SpoIVFB cleaves Pro-σ^K, releasing σ^K into the mother cell to direct transcription. C) RseP is located in the E. coli inner membrane with its tandem PDZ domains in the periplasm. DegS cleaves the periplasmic C-terminal domain of RseA, then RseP cleaves the TMS, releasing the RseA N-terminal domain in complex with σ^E into the cytosol, where ClpXP degrades the rest of RseA, releasing σ^E to direct transcription.