Title : Consensus analysis of
signal peptide peptidase and homologous human
aspartic proteases reveals opposite topology of catalytic
domains compared with presenilins
Abstract :
- The human genome encodes seven intramembrane-cleaving GXGD aspartic proteases
- These are the two presenilins that activate signaling molecules and are implicated in Alzheimer's disease, signal peptide peptidase ( SPP ), required for immune surveillance, and four SPP-like candidate proteases (SPPLs), of unknown function
- Here we describe a comparative analysis of the topologies of SPP and its human homologues, SPPL2a, -2b, -2c, and -3
- We demonstrate that their N-terminal extensions are located in the extracellular space and, except for SPPL3 , are modified with N-glycans
- Whereas SPPL2a , -2b, and -2c contain a signal sequence , SPP and SPPL3 contain a type I signal anchor sequence for initiation of protein translocation and membrane insertion
- The hydrophilic loops joining the transmembrane regions , which contain the catalytic residues , are facing the exoplasm
- The C termini of all these proteins are exposed toward the cytosol
- Taken together, our study demonstrates that SPP and its homologues are all of the same principal structure with a catalytic domain embedded in the membrane in opposite orientation to that of presenilins
- Other than presenilins, SPPL2a, -2b, -2c, and -3 are therefore predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
- 5. SPP, sequence
- 5. SPPL3, sequence
- 5. Whereas SPPL2a, sequence
- 6. -, residues
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):