Stable insertion of Alzheimer Abeta peptide into the ER membrane strongly correlates with its length.
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.
Lundin
Carolina
C
Stockholm Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, Svante Arrhenius väg 12, SE-106 91 Stockholm, Sweden.
Johansson
Sofia
S
Johnson
Arthur E
AE
Näslund
Jan
J
von Heijne
Gunnar
G
Nilsson
IngMarie
I
D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008861:Microsomes / Q000378:metabolism; D008954:Models, Biological; D016254:Mutagenesis, Insertional; D010455:Peptides / Q000737:chemistry / Q000235:genetics*; D015202:Protein Engineering; D017434:Protein Structure, Tertiary
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D010455:Peptides