Linked Life Data

21296884

Source:http://linkedlifedata.com/resource/pubmed/id/21296884

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2011-4-4
pubmed:abstractText
The ?-secretase complex is a member of the family of intramembrane cleaving proteases, involved in the generation of the A? peptides in Alzheimer disease. One of the four subunits of the complex, presenilin, harbors the catalytic site, although the role of the other three subunits is less well understood. Here, we studied the role of the smallest subunit, Pen-2, in vivo and in vitro. We found a profound Notch-deficiency phenotype in Pen-2-/- embryos confirming the essential role of Pen-2 in the ?-secretase complex. We used Pen-2-/- fibroblasts to investigate the structure-function relation of Pen-2 by the scanning cysteine accessibility method. We showed that glycine 22 and proline 27 in hydrophobic domain 1 of Pen-2 are essential for complex formation and stability of ?-secretase. We also demonstrated that hydrophobic domain 1 and the loop domain of Pen-2 are located in a water-containing cavity and are in short proximity to the presenilin C-terminal fragment. We finally demonstrated the essential role of Pen-2 for the proteolytic activity of the complex. Our study supports the hypothesis that Pen-2 is more than a structural component of the ?-secretase complex and may contribute to the catalytic mechanism of the enzyme.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
8
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12271-82
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Functional and topological analysis of Pen-2, the fourth subunit of the gamma-secretase complex.
pubmed:affiliation
Laboratory for the Research of Neurodegenerative Diseases, Center for Human Genetics, KULeuven, Leuven, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't