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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2004-4-6
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pubmed:abstractText |
Presenilin (PS) is the presumptive catalytic component of the intramembrane aspartyl protease gamma-secretase complex. Recently a family of presenilin homologs was identified. One member of this family, signal peptide peptidase (SPP), has been shown to be a protease, which supports the hypothesis that PS and presenilin homologs are related intramembrane-cleaving aspartyl proteases. SPP has been reported as a glycoprotein of approximately 45 kDa. Our initial characterization of SPP isolated from human brain and cell lines demonstrated that SPP is primarily present as an SDS-stable approximately 95-kDa protein on Western blots. Upon heating or treatment of this approximately 95-kDa SPP band with acid, a approximately 45-kDa band could be resolved. Co-purification of two different epitope-tagged forms of SPP from a stably transfected cell line expressing both tagged versions demonstrated that the approximately 95-kDa band is a homodimer of SPP. Pulse-chase metabolic labeling studies demonstrated that the SPP homodimer assembles rapidly and is metabolically stable. In a glycerol velocity gradient, SPP sedimented from approximately 100-200 kDa. Significantly the SPP homodimer was specifically labeled by an active site-directed photoaffinity probe (III-63) for PS, indicating that the active sites of SPP and PS/gamma-secretase are similar and providing strong evidence that the homodimer is functionally active. Collectively these data suggest that SPP exists in vivo as a functional dimer.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid Precursor Protein Secretases,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/BACE1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Glycerol,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PSEN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Trichloroacetic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/signal peptide peptidase
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15153-60
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14704149-Amyloid Precursor Protein Secretases,
pubmed-meshheading:14704149-Animals,
pubmed-meshheading:14704149-Aspartic Acid Endopeptidases,
pubmed-meshheading:14704149-Binding Sites,
pubmed-meshheading:14704149-Blotting, Western,
pubmed-meshheading:14704149-Brain,
pubmed-meshheading:14704149-CHO Cells,
pubmed-meshheading:14704149-Cell Line,
pubmed-meshheading:14704149-Cricetinae,
pubmed-meshheading:14704149-Dimerization,
pubmed-meshheading:14704149-Endopeptidases,
pubmed-meshheading:14704149-Enzyme Inhibitors,
pubmed-meshheading:14704149-Epitopes,
pubmed-meshheading:14704149-Glycerol,
pubmed-meshheading:14704149-Humans,
pubmed-meshheading:14704149-Immunohistochemistry,
pubmed-meshheading:14704149-Membrane Proteins,
pubmed-meshheading:14704149-Precipitin Tests,
pubmed-meshheading:14704149-Presenilin-1,
pubmed-meshheading:14704149-Protein Binding,
pubmed-meshheading:14704149-Protein Structure, Tertiary,
pubmed-meshheading:14704149-Subcellular Fractions,
pubmed-meshheading:14704149-Transfection,
pubmed-meshheading:14704149-Trichloroacetic Acid
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pubmed:year |
2004
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pubmed:articleTitle |
Signal peptide peptidase forms a homodimer that is labeled by an active site-directed gamma-secretase inhibitor.
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pubmed:affiliation |
Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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