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

FEBS Letters

Salim, Samina¹  Terenius, Lars²  Tjernberg, Lars O.²  Oppermann, Udo C.T.¹  Jörnvall, Hans¹ 

[1] Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden;Center for Molecular Medicine, Karolinska Hospital, S-171 76 Stockholm, Sweden

关键词: ERAB;    Short-chain dehydrogenases/reductase;    Hydroxysteroid dehydrogenase;    Alzheimer's disease;    Amyloid β-peptide;    Apoptosis;    Aβ;    amyloid β-peptide;    SDR;    short-chain dehydrogenases/reductases;   

DOI  :  10.1016/S0014-5793(99)00586-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The intracellular amyloid β-peptide (Aβ) 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 Aβ peptide inhibits the enzymatic reaction in a mixed type fashion with a K _i of 1.2 μmol/l and a K _iES of 0.3 μmol/l, using 3-hydroxybutyryl-CoA. The peptide region necessary for inhibition comprises residues 12–24 of Aβ1–40, covering the 16–20 fragment, which is the minimum sequence for the blockade of Aβ 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 Aβ with ERAB further links oxidoreductase activity with both apoptosis and amyloid toxicity.

【 授权许可】

Unknown