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

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.

SUBMITTER: Lundin C

PROVIDER: S-EPMC2000821 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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

Lundin Carolina C Johansson Sofia S Johnson Arthur E AE Näslund Jan J von Heijne Gunnar G Nilsson IngMarie I

FEBS letters 20070719 20

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 r ...[more]

PMID: 17659280

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