The overall structure of the multi-domain amyloid precursor protein

Ina Coburger,S.o. Dahms ,Manuel E. Than

doi:10.1186/1750-1326-8-s1-p55

Abstract

Background The amyloid precursor protein (APP) is a type I transmembrane protein that is expressed in a wide number of different cell types. Proteolytic processing by betaand gamma-secretases releases 38-43 amino acid long peptides, so called Ab amyloid peptides that accumulate within the plaques in the brain of Alzheimer s disease patients. Alternatively, initiation of the proteolysis cascade by alpha-secretase prevents the development of these toxic peptides [1,2]. In spite of intense research regarding the involvement of APP in Alzheimer s disease, The three-dimensional structure of the entire protein, its physiologic function and the regulation of its proteolytic processing remain, however, largely unclear to date [3].

Highlights

The amyloid precursor protein (APP) is a type I transmembrane protein that is expressed in a wide number of different cell types
In spite of intense research regarding the involvement of APP in Alzheimers disease, The three-dimensional structure of the entire protein, its physiologic function and the regulation of its proteolytic processing remain, largely unclear to date [3]
Using limited proteolysis followed by mass spectrometry and Edman degradation as well as analytical gel permeation chromatography coupled static light scattering, we experimentally analyzed the structural domain boundaries

Summary

Background

The amyloid precursor protein (APP) is a type I transmembrane protein that is expressed in a wide number of different cell types. Proteolytic processing by betaand gamma-secretases releases 38-43 amino acid long peptides, so called Ab amyloid peptides that accumulate within the plaques in the brain of Alzheimers disease patients. Initiation of the proteolysis cascade by alpha-secretase prevents the development of these toxic peptides [1,2]. In spite of intense research regarding the involvement of APP in Alzheimers disease, The three-dimensional structure of the entire protein, its physiologic function and the regulation of its proteolytic processing remain, largely unclear to date [3]

Materials and methods

Conclusions

Results