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.
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.
Oppermann
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Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. udo.oppermann@mbb.ki.se
Salim
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Tjernberg
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Terenius
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Jörnvall
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D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D016415:Sequence Alignment
D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human; C458480:Hsd17b10 protein, mouse