Home
Resources
Publications
Structural Investigation of the C-terminal Catalytic Fragment of Presenilin 1

Structural Investigation of the C-terminal Catalytic Fragment of Presenilin 1

Solmaz Sobhanifar, Birgit Schneider, Frank Löhr, Daniel Gottstein, Teppei Ikeya, Krzysztof Mlynarczyk, Wojciech Pulawski, Umesh Ghoshdastider, Michal Kolinski, Slawomir Filipek, Peter Güntert, Frank Bernhard, etc.

Proc Natl Acad Sci U S A. 2010 May 25;107(21):9644-9.

PMID: 20445084

Abstract:

The gamma-secretase complex has a decisive role in the development of Alzheimer's disease, in that it cleaves a precursor to create the amyloid beta peptide whose aggregates form the senile plaques encountered in the brains of patients. Gamma-secretase is a member of the intramembrane-cleaving proteases which process their transmembrane substrates within the bilayer. Many of the mutations encountered in early onset familial Alzheimer's disease are linked to presenilin 1, the catalytic component of gamma-secretase, whose active form requires its endoproteolytic cleavage into N-terminal and C-terminal fragments. Although there is general agreement regarding the topology of the N-terminal fragment, studies of the C-terminal fragment have yielded ambiguous and contradictory results that may be difficult to reconcile in the absence of structural information. Here we present the first structure of the C-terminal fragment of human presenilin 1, as obtained from NMR studies in SDS micelles. The structure reveals a topology where the membrane is likely traversed three times in accordance with the more generally accepted nine transmembrane domain model of presenilin 1, but contains unique structural features adapted to accommodate the unusual intramembrane catalysis. These include a putative half-membrane-spanning helix N-terminally harboring the catalytic aspartate, a severely kinked helical structure toward the C terminus as well as a soluble helix in the assumed-to-be unstructured N-terminal loop.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248117	Presenilin-1 N-Terminal Peptide			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: