Pregled bibliografske jedinice broj: 415736
A presenilin dimer at the core of the gamma-secretase enzyme : insights from parallel analysis of Notch 1 and APP proteolysis
A presenilin dimer at the core of the gamma-secretase enzyme : insights from parallel analysis of Notch 1 and APP proteolysis // Proceedings of the National Academy of Sciences of the United States of America, 100 (2003), 22; 13075-13080 doi:10.1073/pnas.1735338100 (međunarodna recenzija, članak, znanstveni)
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Naslov
A presenilin dimer at the core of the gamma-secretase enzyme : insights from parallel analysis of Notch 1 and APP proteolysis
Autori
Schroeter, E.H. ; Ilagan, M.X.G. ; Brunkan, A.L. ; Hećimović, Silva ; Li, Y-M ; Xu, M. ; Lewis, H.D. ; Saxena, M.T. ; De Strooper, B. ; Coonrod, A. ; Tomita, T. ; Iwatsubo, T. ; Moore, C.L. ; Shearman, M. ; Goate, A. ; Wolfe, M.S. ; Kopan, R.
Izvornik
Proceedings of the National Academy of Sciences of the United States of America (0027-8424) 100
(2003), 22;
13075-13080
Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni
Ključne riječi
Alzheimer’ s disease ; amyloid-beta ; APP ; Notch ; gamma-secretase
Sažetak
Notch receptors and the amyloid precursor protein are type I membrane proteins that are proteolytically cleaved within their transmembrane domains by a presenilin (PS)-dependent gamma-secretase activity. In both proteins, two peptide bonds are hydrolyzed: one near the inner leaflet and the other in the middle of the transmembrane domain. Under saturating conditions the substrates compete with each other for proteolysis, but not for binding to PS. At least some Alzheimer's disease-causing PS mutations reside in proteins possessing low catalytic activity. We demonstrate (i) that differentially tagged PS molecules coimmunoprecipitate, and (ii) that PS N-terminal fragment dimers exist by using a photoaffinity probe based on a transition state analog gamma-secretase inhibitor. We propose that gamma-secretase contains a PS dimer in its catalytic core, that binding of substrate is at a site separate from the active site, and that substrate is cleaved at the interface of two PS molecules.
Izvorni jezik
Engleski
Znanstvena područja
Temeljne medicinske znanosti
POVEZANOST RADA
Ustanove:
Institut "Ruđer Bošković", Zagreb
Profili:
Silva Katušić Hećimović
(autor)
Citiraj ovu publikaciju:
Časopis indeksira:
- Current Contents Connect (CCC)
- Web of Science Core Collection (WoSCC)
- Science Citation Index Expanded (SCI-EXP)
- SCI-EXP, SSCI i/ili A&HCI
- Scopus
- MEDLINE
- EconLit