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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


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. et al.
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

Citiraj ovu publikaciju

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. et al.
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)
Schroeter, E., Ilagan, M., Brunkan, A., Hećimović, S., Li, Y., Xu, M., Lewis, H., Saxena, M., De Strooper, B. & Coonrod, A. (2003) 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 (22), 13075-13080 doi:10.1073/pnas.1735338100.
@article{article, year = {2003}, pages = {13075-13080}, DOI = {10.1073/pnas.1735338100}, keywords = {Alzheimer’ s disease, amyloid-beta, APP, Notch, gamma-secretase}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, doi = {10.1073/pnas.1735338100}, volume = {100}, number = {22}, issn = {0027-8424}, title = {A presenilin dimer at the core of the gamma-secretase enzyme : insights from parallel analysis of Notch 1 and APP proteolysis}, keyword = {Alzheimer’ s disease, amyloid-beta, APP, Notch, gamma-secretase} }
@article{article, year = {2003}, pages = {13075-13080}, DOI = {10.1073/pnas.1735338100}, keywords = {Alzheimer’ s disease, amyloid-beta, APP, Notch, gamma-secretase}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, doi = {10.1073/pnas.1735338100}, volume = {100}, number = {22}, issn = {0027-8424}, title = {A presenilin dimer at the core of the gamma-secretase enzyme : insights from parallel analysis of Notch 1 and APP proteolysis}, keyword = {Alzheimer’ s disease, amyloid-beta, APP, Notch, gamma-secretase} }

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


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