Binding of amyloid beta-peptide to mitochondrial hydroxyacyl-CoA dehydrogenase (ERAB): regulation of an SDR enzyme activity with implications for apoptosis in Alzheimer's disease.

Journal article

The intracellular amyloid beta-peptide (A beta) binding protein, ERAB, a member of the short-chain dehydrogenase/reductase (SDR) family, is known to mediate apoptosis in different cell lines and to be a class II hydroxyacyl-CoA dehydrogenase. The A beta peptide inhibits the enzymatic reaction in a mixed type fashion with a Ki of 1.2 micromol/l and a KiES of 0.3 micromol/l, using 3-hydroxybutyryl-CoA. The peptide region necessary for inhibition comprises residues 12-24 of A beta1-40, covering the 16-20 fragment, which is the minimum sequence for the blockade of A beta polymerization, but that minimal fragment is not sufficient for more than marginal inhibition. The localization of ERAB to the endoplasmic reticulum and mitochondria suggests a complex interaction with components of the programmed cell death machinery. The interaction of A beta with ERAB further links oxidoreductase activity with both apoptosis and amyloid toxicity.

Authors: Oppermann, U; Salim, S; Tjernberg, L; Terenius, L; Jörnvall, H

• Journal: FEBS letters
• Volume: 451
• Issue: 3
• Pages: 238-242
• Publication date: 1999-05-01
• DOI: 10.1016/s0014-5793(99)00586-4
• EISSN: 1873-3468
• ISSN: 0014-5793
• Language: English
• Keywords: Molecular Sequence Data; Amyloid beta-Peptides; Carrier Proteins; Humans; Amino Acid Sequence; 3-Hydroxyacyl CoA Dehydrogenases; Apoptosis; Enzyme Activation; Sequence Alignment; Alzheimer Disease; Mitochondria