Source:http://linkedlifedata.com/resource/pubmed/id/16234244
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
51
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pubmed:dateCreated |
2005-12-19
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pubmed:abstractText |
gamma-Secretase is a multimeric membrane protein complex comprised of presenilin (PS), nicastrin (Nct), Aph-1, and Pen-2. It is a member of an atypical class of aspartic proteases that hydrolyzes peptide bonds within the membrane. During the biosynthetic process of the gamma-secretase complex, Nct and Aph-1 form a heterodimeric intermediate complex and bind to the C-terminal region of PS, serving as a stabilizing scaffold for the complex. Pen-2 is then recruited into this trimeric complex and triggers endoproteolysis of PS, conferring gamma-secretase activity. Although the Pen-2 accumulation depends on PS, the binding partner of Pen-2 within the gamma-secretase complex remains unknown. We reconstituted PS1 in Psen1/Psen2 deficient cells by expressing a series of PS1 mutants in which one of the N-terminal six transmembrane domains (TMDs) was swapped with those of CD4 (a type I transmembrane protein) or CLAC-P (a type II transmembrane protein). We report that the proximal two-thirds of TMD4 of PS1, including the conserved Trp-Asn-Phe sequence, are required for its interaction with Pen-2. Using a chimeric CD4 molecule harboring PS1 TMD4, we further demonstrate that the PS1 TMD4 bears a direct binding motif to Pen-2. Pen-2 may contribute to the activation of the gamma-secretase complex by directly binding to the TMD4 of PS1.
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pubmed:language |
eng
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pubmed:journal | |
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/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PSEN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PSENEN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
41967-75
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16234244-Amino Acid Sequence,
pubmed-meshheading:16234244-Amyloid Precursor Protein Secretases,
pubmed-meshheading:16234244-Aspartic Acid Endopeptidases,
pubmed-meshheading:16234244-Cell Line,
pubmed-meshheading:16234244-Cell Membrane,
pubmed-meshheading:16234244-Endopeptidases,
pubmed-meshheading:16234244-Humans,
pubmed-meshheading:16234244-Hydrolysis,
pubmed-meshheading:16234244-Membrane Proteins,
pubmed-meshheading:16234244-Molecular Sequence Data,
pubmed-meshheading:16234244-Plasmids,
pubmed-meshheading:16234244-Presenilin-1,
pubmed-meshheading:16234244-Protein Binding,
pubmed-meshheading:16234244-Sequence Homology, Amino Acid
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pubmed:year |
2005
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pubmed:articleTitle |
Pen-2 is incorporated into the gamma-secretase complex through binding to transmembrane domain 4 of presenilin 1.
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pubmed:affiliation |
Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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