dc.contributor.author | Dev, Kumlesh | |
dc.date.accessioned | 2019-08-26T08:39:46Z | |
dc.date.available | 2019-08-26T08:39:46Z | |
dc.date.issued | 2004 | |
dc.date.submitted | 2004 | en |
dc.identifier.citation | Friedmann, E., Lemberg, M.K., Weihofen, A., Dev, K.K., Dengler, U., Rovelli, G., Martoglio, B. Consensus analysis of Signal Peptide Peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared to Presenilins, Journal of Biological Chemistry, 2004, 279, 49, 50790-50798 | en |
dc.identifier.other | Y | |
dc.identifier.other | doi:10.1074/jbc.M407898200 | |
dc.identifier.uri | http://www.jbc.org/content/279/49/50790.full | |
dc.identifier.uri | http://hdl.handle.net/2262/89311 | |
dc.description | PUBLISHED | en |
dc.description.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. | en |
dc.format.extent | 50790 | en |
dc.format.extent | 50798 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | J. Biol Chem; | |
dc.relation.ispartofseries | 279; | |
dc.rights | Y | en |
dc.subject | Alzheimer’s disease | en |
dc.subject | Preselinins | en |
dc.subject | Intramembrane-cleaving GXGD aspartic proteases | en |
dc.subject | Signal peptide pepti-dase (SPP) | en |
dc.subject | SPP-like candidate proteases (SPPLs) | en |
dc.title | Consensus analysis of Signal Peptide Peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared to Presenilins | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/devk | |
dc.identifier.rssinternalid | 57113 | |
dc.rights.ecaccessrights | openAccess | |
dc.subject.TCDTheme | Neuroscience | en |