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PMID: 17659280 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Stable insertion of Alzheimer Abeta peptide into the ER membrane strongly correlates with its length.

FEBS letters ·Vol. 581 ·No. 20 ·2007-08-07 ·Pages 3809-13

Lundin C, Johansson S, Johnson AE, Näslund J, von Heijne G, Nilsson I

Abstract

Alzheimer's disease is characterized by the deposition of amyloid beta-peptide (Abeta) plaques in the brain. Full-length amyloid-beta precursor protein (APP) is processed by alpha- and beta-secretases to yield soluble APP derivatives and membrane-bound C-terminal fragments, which are further processed by gamma-secretase to a non-amyloidogenic 3 kDa product or to Abeta fragments. As different Abeta fragments contain different parts of the APP transmembrane helix, one may speculate that they are retained more or less efficiently in the membrane. Here, we use the translocon-mediated insertion of different APP-derived polypeptide segments into the endoplasmic reticulum membrane to assess the propensities for membrane retention of Abeta fragments. Our results show a strong correlation between the length of an Abeta-derived segment and its ability to integrate into the microsomal membrane.

MeSH Terms
Alzheimer Disease/genetics Amyloid beta-Protein Precursor/chemistry,genetics Endoplasmic Reticulum/genetics Membrane Proteins/genetics Microsomes/metabolism Models, Biological Mutagenesis, Insertional Peptides/chemistry,genetics Protein Engineering Protein Structure, Tertiary
Chemicals
Amyloid beta-Protein Precursor Membrane Proteins Peptides
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lundin Carolina
Stockholm Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, Svante Arrhenius väg 12, SE-106 91 Stockholm, Sweden.
Johansson Sofia
Johnson Arthur E
Näslund Jan
von Heijne Gunnar
Nilsson IngMarie
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Article Info
Journal
FEBS letters
Abbr.
FEBS Lett
ISSN
0014-5793
DOI
10.1016/j.febslet.2007.07.003
Published
2007-08-07
Epub
2007-00-19
Pages
3809-13
Language
English
Region
England
NLM ID
0155157
PMCID
PMC2000821
Subset
IM
Grants
NIGMS NIH HHS · R01 GM026494 · United States
NIGMS NIH HHS · R01 GM026494-26 · United States
NIGMS NIH HHS · R01 GM026494-27 · United States
NIGMS NIH HHS · GM26494 · United States
External Links
PubMed source DOI: 10.1016/j.febslet.2007.07.003 PMC Full Text View journal details
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